CN114520070A - Nerve electrical stimulation electrode and preparation method thereof - Google Patents
Nerve electrical stimulation electrode and preparation method thereof Download PDFInfo
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- A61B5/25—Bioelectric electrodes therefor
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- A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
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Abstract
The application relates to a nerve electrical stimulation electrode and a preparation method thereof, wherein the method comprises the steps of obtaining a silicon substrate; forming a sacrificial layer on a silicon substrate; forming a first flexible substrate layer on the sacrificial layer under the condition of a first spin coating process; forming an electrode array on the first flexible substrate layer; each electrode in the electrode array is made of chromium-platinum alloy material; forming a second flexible substrate layer on the electrode array under the second spin coating process condition; the thickness of the second flexible substrate layer is larger than that of each electrode; forming a hard mask layer on the second flexible substrate layer; etching the hard mask layer and the second flexible substrate layer to expose partial surfaces of the electrodes; removing the hard mask layer, and releasing the sacrificial layer to enable the silicon substrate to fall off, so as to obtain the nerve electrical stimulation electrode; and carrying out electrochemical treatment on the nerve electrical stimulation electrode to form an electrode modification layer on the surface of each electrode, and obtaining the nerve electrical stimulation electrode after the electrochemical treatment. The reliability and the safety of the nerve electrical stimulation electrode can be improved.
Description
Technical Field
The application relates to the technical field of nerve electrodes, in particular to a nerve electrical stimulation electrode and a preparation method thereof.
Background
The acquisition of neuron electrical signals mainly depends on brain electrodes, and the neuron electrical signals are generally divided into non-invasive scalp brain electrodes, semi-invasive cortical brain electrodes and invasive deep electrodes according to different implantation positions and information acquisition modes, wherein the deep brain electrodes are directly implanted into the deep part of the brain, and the spatial distance from the deep brain electrodes to target neurons enables the deep brain electrodes to have higher spatial resolution, detection accuracy and signal-to-noise ratio.
The application of stimulation to the brain is an important method for analyzing brain cognitive causality, and brain function is analyzed by synchronously recording corresponding neuron activities. Therefore, it is important to design an electrode with a specific stimulation function.
Disclosure of Invention
The embodiment of the application provides a nerve electrical stimulation electrode and a preparation method thereof, and the technical scheme is as follows:
according to a first aspect of embodiments of the present application, there is provided a method for preparing a neural electrical stimulation electrode, including:
obtaining a silicon substrate;
forming a sacrificial layer on a silicon substrate;
forming a first flexible substrate layer on the sacrificial layer under the condition of a first spin coating process;
forming an electrode array on the first flexible substrate layer; each electrode in the electrode array is made of chromium-platinum alloy material;
forming a second flexible substrate layer on the electrode array under the second spin coating process condition; the thickness of the second flexible substrate layer is larger than that of each electrode;
forming a hard mask layer on the second flexible substrate layer;
etching the hard mask layer and the second flexible substrate layer to expose partial surfaces of the electrodes;
removing the hard mask layer, and releasing the sacrificial layer to enable the silicon substrate to fall off, so as to obtain the nerve electrical stimulation electrode;
and carrying out electrochemical treatment on the nerve electrical stimulation electrode to form an electrode modification layer on the surface of each electrode, and obtaining the nerve electrical stimulation electrode after electrochemical treatment.
Optionally, the electrical nerve stimulation electrode is subjected to electrochemical treatment to form an electrode modification layer on the surface of each electrode, including:
placing the nerve electrical stimulation electrode in electrolyte of a three-electrode system electrochemical treatment device; the electrolyte is a prepolymer or solution of a high polymer material;
the nerve electrical stimulation electrode is used as a working electrode, an electric signal is applied, and after the preset duration of treatment, an electrode modification layer is formed on the surface of each electrode.
Optionally, forming a first flexible substrate layer on the sacrificial layer under the first spin-coating process condition includes:
a first SU8 substrate layer was spin coated on the sacrificial layer using a spin speed of 3000rpm/min and a spin time of 30 seconds.
Optionally, forming a second flexible substrate layer on the electrode array under a second spin-coating process condition includes:
a second SU8 substrate layer was spin coated on the electrode array using a spin coating speed of 3000rpm/min and a spin coating time of 30 seconds.
Optionally, before forming the electrode array on the first flexible substrate layer, the method further includes:
depositing a first photoresist layer on the first flexible substrate layer;
patterning the first photoresist layer;
depositing a first metal layer on the first photoresist layer after the patterning treatment in a thermal evaporation mode; the first metal layer is chrome-gold alloy;
and stripping the first photoresist layer and the first metal layer on the surface of the first photoresist layer to obtain the metal interconnection line.
Optionally, forming an electrode array on the first flexible substrate layer includes:
forming an SU8 isolation layer on the first flexible substrate layer;
depositing a second photoresist layer on the SU8 isolation layer;
patterning the second photoresist layer;
depositing a second metal layer on the patterned second photoresist layer in a sputtering mode; the second metal layer is chromium-platinum alloy;
and stripping the second photoresist layer and the second metal layer on the surface of the second photoresist layer to obtain the required electrode array.
Optionally, the electrolyte is a prepolymer or solution of any one of iridium, graphene and carbon nanotubes.
Optionally, the second metal layer includes a chromium layer and a platinum layer; the thickness of the chromium layer is 10 nanometers; the thickness of the platinum layer was 100 nm.
Optionally, the thickness of the first SU8 substrate layer or the second SU8 substrate layer is 500 nanometers.
According to a second aspect of the embodiments of the present application, there is provided a neural electrical stimulation electrode prepared by the method for preparing a neural electrical stimulation electrode provided by the first aspect of the embodiments of the present application.
The nerve electrical stimulation electrode and the preparation method thereof provided by the embodiment of the application have the following beneficial effects:
on one hand, platinum is used for replacing gold as an electrode material, and due to the fact that platinum has good electrochemical stability, the neural electrode can be prevented from being damaged by dissolution during electrical stimulation, safety and reliability of electrical stimulation by using the electrode can be improved, and the platinum electrode has potential application to clinical experiments. On the other hand, the nerve electrode is modified by an electrochemical method, so that the impedance of the electrode can be reduced, the current/voltage used by electric stimulation can be reduced, and the safety of electric stimulation by using the electrode can be improved. The nerve electrical stimulation electrode has two functions of recording and electrical stimulation, the application flexibility is greatly improved, and repeated implantation can be avoided.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
Fig. 1 is a schematic flow chart of a method for manufacturing a neural electrical stimulation electrode according to an embodiment of the present application;
FIGS. 2(a) - (h) are schematic diagrams of a process for preparing a neural electric stimulation electrode according to an embodiment of the present application;
fig. 3 is a schematic flow chart of a method for manufacturing a neural electrical stimulation electrode according to an embodiment of the present application;
fig. 4(a) is a schematic diagram of forming an SU8 isolation layer on a first flexible substrate layer according to an embodiment of the present application;
fig. 4(b) is a schematic diagram of stripping the second photoresist layer and the second metal layer on the surface of the second photoresist layer to obtain the desired electrode array according to the embodiment of the present application.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all of the embodiments. All other embodiments obtained by a person of ordinary skill in the art based on the embodiments in the present application without making creative efforts shall fall within the protection scope of the present application.
It should be noted that the terms "first," "second," and the like in the description and claims of this application and in the drawings described above are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the application described herein are capable of operation in sequences other than those illustrated or described herein. Furthermore, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or server that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
In the related technology, the stimulating electrode usually selects gold as the material of the electrode array, the electrode can stably collect nerve electrical signals, but in the occasion of nerve stimulation, due to the electrochemical property of gold, when certain current or voltage is applied to the electrode for stimulation, the gold can be dissolved in environmental liquid and release toxic free heavy metal, which can cause the defect failure of the electrode and can not record the electrical signals or stimulation continuously; furthermore, current stimulation electrodes tend to require the application of larger currents/voltages, which results in lower safety of the neural electrodes.
In view of this, embodiments of the present application provide a neural electrical stimulation electrode and a method for manufacturing the same, which can improve reliability and safety of the neural electrical stimulation electrode.
A specific embodiment of a method for manufacturing a neurostimulation electrode of the present application is described below, fig. 1 is a schematic flow chart of a method for manufacturing a neurostimulation electrode provided by the present application, and fig. 2(a) - (h) are schematic diagrams of a process for manufacturing a neurostimulation electrode provided by the present application, and specifically as shown in fig. 1 and fig. 2, the method may include:
in step S101, as shown in fig. 2(a), a silicon substrate 200 is obtained.
In step S103, as shown in fig. 2(b), a sacrificial layer 201 is formed on the silicon substrate 200.
In step S105, as shown in fig. 2(c), a first flexible substrate layer 202 is formed on the sacrificial layer 201 under the first spin-coating process condition.
In step S107, as shown in fig. 2(d), an electrode array is formed on the first flexible substrate layer 202; each electrode 203 in the electrode array is made of a chromium-platinum alloy material.
In step S109, as shown in fig. 2(e), under the second spin-coating process condition, a second flexible substrate layer 204 is formed on the electrode array; the thickness of the second flexible substrate layer 204 is larger than the thickness of the electrodes 203.
In step S111, as shown in fig. 2(f), a hard mask layer 205 is formed on the second flexible substrate layer 204;
in step S113, as shown in fig. 2(g), the hard mask layer 205 and the second flexible substrate layer 204 are etched to expose a part of the surface of each electrode 203.
In step S115, as shown in fig. 2(h), the hard mask layer 205 is removed, and the sacrificial layer 201 is released, so that the silicon substrate 200 falls off, and the neural electrical stimulation electrode is obtained.
In step S117, the electrostimulation neural electrode is electrochemically processed to form an electrode modification layer on the surface of each electrode 203, and the electrostimulation neural electrode after electrochemical processing is obtained.
In the embodiment of the application, the nerve electrical stimulation electrode is prepared through the steps of S101 to S117, on one hand, platinum is used to replace gold as an electrode material, and because platinum has good electrochemical stability, the nerve electrode can be prevented from being damaged by dissolution during electrical stimulation, the safety and reliability of electrical stimulation by using the electrode can be improved, and the method has potential application in clinical experiments. On the other hand, the nerve electrode is modified by an electrochemical method, so that the impedance of the electrode can be reduced, the current/voltage used by electric stimulation can be reduced, and the safety of electric stimulation by using the electrode can be improved. The nerve electrical stimulation electrode has two functions of recording and electrical stimulation, the application flexibility is greatly improved, and repeated implantation can be avoided.
In an alternative embodiment, in step S117, performing electrochemical treatment on the neurostimulation electrode to form an electrode modification layer on the surface of each electrode, may include the following steps:
in step S1171, the neural electric stimulation electrode is placed in an electrolyte of the three-electrode system electrochemical processing device; the electrolyte is prepolymer or solution of high molecular material.
The electrolyte can be a prepolymer or a solution of any one of iridium, graphene and carbon nanotubes.
In step S1173, the neuro-electro-stimulation electrode is used as a working electrode, an electrical signal is applied, and after a preset duration of processing, an electrode modification layer is formed on the surface of each electrode.
In one particular embodiment, the electrochemical treatment is carried out using a galvanostatic mode, with a limiting voltage of less than 0.8V. When the modification material is platinum black, the current is set to 80nA for 40 seconds; when the modifying material was PEDOT, the current was set at 10nA for 10 seconds.
In the above embodiment, the surface of the electrode is modified by an electrochemical method, so that the impedance of the electrode is reduced from megaohms to kiloohms, and thus, a smaller current can be used for stimulation, thereby improving the safety of electrical stimulation by using the electrode.
In an optional embodiment, in the step S105, under the condition of the first spin coating process, forming the first flexible substrate layer on the sacrificial layer may specifically include: a first SU8 substrate layer was spin coated on the sacrificial layer using a spin speed of 3000rpm/min and a spin time of 30 seconds.
Accordingly, the thickness of the first SU8 substrate layer is 500 nm.
In the embodiment of the application, the first spin-coating process condition comprises spin-coating speed and spin-coating time; different thicknesses of the first flexible substrate layer can be obtained through different spin coating speeds and spin coating times. Wherein the material of the first flexible substrate layer may be polyimide in addition to SU8 mentioned in the above embodiments.
In an alternative embodiment, in the step S109, under the second spin coating process condition, forming a second flexible substrate layer on the electrode array may specifically include: a second SU8 substrate layer was spin coated on the electrode array using a spin coating speed of 3000rpm/min and a spin coating time of 30 seconds.
Correspondingly, the thickness of the second SU8 substrate layer was 500 nm.
In the embodiment of the application, the second spin-coating process condition comprises spin-coating speed and spin-coating time; through different spin coating speeds and spin coating times, second flexible substrate layers with different thicknesses can be obtained. Wherein the material of the second flexible substrate layer may be polyimide in addition to SU8 mentioned in the above embodiments. The material of the second flexible substrate layer is the same as the material of the first flexible substrate layer.
In an alternative embodiment, before the step S107, the preparation method further includes the following steps as shown in fig. 3:
in step S1061, depositing a first photoresist layer on the first flexible substrate layer;
in step S1063, a patterning process is performed on the first photoresist layer;
in step S1065, depositing a first metal layer on the patterned first photoresist layer by thermal evaporation; the first metal layer is chrome-gold alloy;
in a specific embodiment, the first photoresist layer is patterned by photolithography, and then a first metal layer of a chrome-gold structure is thermally vapor deposited and patterned by a lift-off process to obtain the metal interconnection line. The thickness of the chromium layer in the first metal layer may be 10nm, and correspondingly, the thickness of the gold layer in the first metal layer may be 100 nm.
In step S1067, the first photoresist layer and the first metal layer on the surface of the first photoresist layer are stripped, so as to obtain a metal interconnection line.
The metal interconnection lines are used for transmitting the nerve electrical signals collected by the electrodes to the rear-end collecting unit for further analysis and processing.
Accordingly, in an alternative embodiment, after obtaining the metal interconnection line, in step S107, forming an electrode array on the first flexible substrate layer may specifically include the following steps:
in step S1071, an SU8 isolation layer 206 is formed on the first flexible substrate layer 202;
as shown in fig. 4(a), fig. 4(a) is a schematic diagram of forming an SU8 isolation layer 206 on a first flexible substrate layer 202 according to an embodiment of the present application. Wherein the thickness of the SU8 isolation layer 206 is greater than the thickness of the metal interconnect line 207;
in step S1073, a second photoresist layer is deposited over SU8 isolation layer 206;
in step S1075, the second photoresist layer is subjected to patterning processing;
in step S1077, a second metal layer is deposited on the patterned second photoresist layer by sputtering; the second metal layer is chromium-platinum alloy;
in a specific embodiment, the second metal layer comprises a chromium layer and a platinum layer; and patterning the second photoresist layer by photoetching, sputtering a second metal layer with a chromium-platinum structure, and patterning by a stripping process to obtain the metal electrode. Wherein the thickness of the chromium layer in the second metal layer may be 10nm, and correspondingly, the thickness of the platinum layer in the second metal layer may be 100 nm.
In step S1079, the second photoresist layer and the second metal layer on the surface of the second photoresist layer are stripped to obtain the desired electrode array.
As shown in fig. 4(b), fig. 4(b) is a schematic diagram of stripping the second photoresist layer and the second metal layer on the surface of the second photoresist layer to obtain the desired electrode array according to the embodiment of the present application.
In a specific embodiment, a 400 μm thick silicon substrate is obtained and cleaned; depositing a 100 nm-thick nickel sacrificial layer on the surface of the silicon substrate through thermal evaporation; spin-coating for 30s at a spin-coating speed of 3000r/min to prepare a first SU8 substrate layer with the thickness of 500 nm; patterning the photoresist by photoetching, depositing a layer of 10nm/100nm thick chromium/gold alloy by thermal evaporation, and patterning by a stripping process to obtain a metal interconnection line; spin-coating for 30s at a spin-coating speed of 3000r/min to prepare an isolation layer with the thickness of 500nm, and patterning by photoetching to obtain a flexible SU8 isolation layer between an electrode layer and a metal interconnection layer; patterning the photoresist by photoetching, sputtering and plating a layer of 10nm/100nm thick chromium/platinum alloy, and patterning by a stripping process to obtain a metal electrode; spin-coating for 30s at a spin-coating speed of 3000r/min to prepare a second SU8 substrate layer with a thickness of 500 nm; and etching to remove the nickel sacrificial layer and releasing the nerve electrical stimulation electrode from the silicon substrate.
In the embodiment of the application, a flexible polymer material is used as a substrate through an MEMS micro-processing technology, a metal lead and an electrode are manufactured through a metallization technology and a photoetching technology, and the flexible probe part is stripped from a silicon chip through an etching sacrificial layer, so that the nerve electrical stimulation electrode is obtained. In the experimental process, the nerve electrical stimulation electrode is implanted into a selected mouse brain area, and the electrode is led out through flexible connection at the rear end and connected with the rear end circuit and the control system. The flexible electrode selects a channel to give electric stimulation, and other channels record electric signals of the nerve activity at the same time of stimulation and after the stimulation is finished, and transmit the electric signals to the back end for analysis.
In the embodiment of the application, the nerve electrical stimulation electrode is prepared by the preparation method introduced in the embodiment, the nerve electrical stimulation electrode can be used for electrophysiological signal recording of nerve activity and nerve electrical stimulation, the nerve electrical stimulation and the nerve electrophysiological recording are realized by using the electrode, and the normal activity of a neuron at a certain specific point can be accurately measured or stimulated. Through the research on the neuron stimulation mechanism, the development of sensory reconstruction technology and the like is assisted.
The embodiment of the application also provides a nerve electrical stimulation electrode which is prepared by the preparation method embodiment of the application.
The nerve electrical stimulation electrode and the preparation method of the nerve electrical stimulation electrode in the embodiment of the application are based on the same application concept.
It should be noted that: the sequence of the embodiments of the present application is only for description, and does not represent the advantages and disadvantages of the embodiments. And specific embodiments thereof have been described above. Other embodiments are within the scope of the following claims. In some cases, the actions or steps recited in the claims may be performed in a different order than in the embodiments and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results. In some embodiments, multitasking and parallel processing may also be possible or may be advantageous.
The embodiments in the present specification are described in a progressive manner, and the same and similar parts among the embodiments are referred to each other, and each embodiment focuses on the differences from the other embodiments. In particular, for the apparatus embodiment, since it is substantially similar to the method embodiment, the description is relatively simple, and for the relevant points, reference may be made to the partial description of the method embodiment.
The above description is only exemplary of the present application and should not be taken as limiting the present application, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present application should be included in the protection scope of the present application.
Claims (10)
1. A preparation method of a nerve electrical stimulation electrode is characterized by comprising the following steps:
obtaining a silicon substrate;
forming a sacrificial layer on the silicon substrate;
forming a first flexible substrate layer on the sacrificial layer under the condition of a first spin coating process;
forming an electrode array on the first flexible substrate layer; each electrode in the electrode array is made of a chromium-platinum alloy material;
forming a second flexible substrate layer on the electrode array under a second spin-coating process condition; the thickness of the second flexible substrate layer is larger than that of each electrode;
forming a hard mask layer on the second flexible substrate layer;
etching the hard mask layer and the second flexible substrate layer to expose partial surfaces of the electrodes;
removing the hard mask layer, and releasing the sacrificial layer to enable the silicon substrate to fall off, so as to obtain a nerve electrical stimulation electrode;
and carrying out electrochemical treatment on the nerve electrical stimulation electrode to form an electrode modification layer on the surface of each electrode, and obtaining the nerve electrical stimulation electrode after electrochemical treatment.
2. The preparation method of claim 1, wherein the step of subjecting the electrostimulation neural electrode to electrochemical treatment to form an electrode modification layer on the surface of each electrode comprises:
placing the nerve electrical stimulation electrode in electrolyte of a three-electrode system electrochemical treatment device; the electrolyte is a prepolymer or solution of a high polymer material;
and applying an electric signal by taking the nerve electric stimulation electrode as a working electrode, and forming an electrode modification layer on the surface of each electrode after processing for a preset time.
3. The method of claim 1, wherein the forming a first flexible substrate layer on the sacrificial layer under the first spin-on process condition comprises:
a first SU8 substrate layer was spin coated on the sacrificial layer using a spin speed of 3000rpm/min and a spin time of 30 seconds.
4. The method of claim 3, wherein forming a second flexible substrate layer on the electrode array under the second spin-on process condition comprises:
a second SU8 substrate layer was spin coated on the electrode array using a spin coating speed of 3000rpm/min and a spin coating time of 30 seconds.
5. The method of manufacturing according to claim 1, wherein prior to forming the electrode array on the first flexible substrate layer, further comprising:
depositing a first photoresist layer on the first flexible substrate layer;
patterning the first photoresist layer;
depositing a first metal layer on the first photoresist layer after the patterning treatment in a thermal evaporation mode; the first metal layer is made of chrome-gold alloy;
and stripping the first photoresist layer and the first metal layer on the surface of the first photoresist layer to obtain the metal interconnection line.
6. The method of manufacturing according to claim 5, wherein forming an array of electrodes on the first flexible substrate layer comprises:
forming an SU8 isolation layer on the first flexible substrate layer;
depositing a second photoresist layer on the SU8 isolation layer;
patterning the second photoresist layer;
depositing a second metal layer on the patterned second photoresist layer in a sputtering mode; the second metal layer is chromium-platinum alloy;
and stripping the second photoresist layer and the second metal layer on the surface of the second photoresist layer to obtain the required electrode array.
7. The method according to claim 2, wherein the electrolyte is a prepolymer or a solution of any one of iridium, graphene, and carbon nanotubes.
8. The production method according to claim 6, wherein the second metal layer includes a chromium layer and a platinum layer; the thickness of the chromium layer is 10 nanometers; the thickness of the platinum layer is 100 nanometers.
9. The method of manufacturing of claim 3 or 4, wherein the thickness of the first SU8 substrate layer or the second SU8 substrate layer is 500 nanometers.
10. A neural electric stimulation electrode prepared by the preparation method of any one of claims 1 to 9.
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