Space electrode preparation method based on focused ion beam and electrode

Abstract

The invention discloses a focused ion beam-based space electrode preparation method, which comprises the following steps of: drawing a metal wire to form a plurality of electrode wires with preset lengths and preset diameters, firmly adhering the electrode wires by using glue, fixing the electrode wires to auxiliary equipment around the electrode wires, anticlockwise rotating the electrode wires for a plurality of circles, then clockwise rotating the electrode wires for a plurality of circles, and finally cutting off the front ends of the electrode wires in a flush manner to form thin wires; the plurality of groups of insulating sleeves are aligned and arranged into a row and are fixed on the electrode bracket, the plurality of groups of filaments respectively penetrate through the plurality of groups of insulating sleeves, the front ends of the filaments are flush, and the tail ends of the plurality of groups of filaments are respectively connected with connector interfaces and are fixed by soldering tin; focusing an ion beam into a microdissection beam by using an electrostatic lens to punch the filament, exposing a local cylindrical surface of the electrode wire as a contact, and sealing the end part of the filament by using photosensitive resin; the connector interface and the electrode support are fixed, a plurality of groups of perforated filaments penetrate into the polyamideamine tube respectively, the rear ends of the perforated filaments are fixed, the portion, close to the connector interface, of the filament is unwound, the insulating sleeve layer is stripped, and one end of the filament penetrates through the REF hole of the PCB and is welded.

Description

Technical Field

[0001] The invention relates to the technical field of power system operation and dispatching automation, and in particular to a method for preparing a space electrode based on a focused ion beam. Background Art

[0002] Brain-computer interface (BCI) technology builds a communication bridge between the brain and artificial devices. One of the important functions of BCI is to decipher brain information. Animals with special sensing capabilities are used as biosensors to extract useful information by deciphering the neurophysiological signals of the relevant sensory cortex. For example, by decoding the electrophysiological signals in the olfactory or taste system of rodents, very low concentrations of chemicals can be detected. Odor detection plays an important role in social security prevention such as food safety control, environmental testing, drug enforcement, and explosives search. The recording electrode in the BCI is a key component that connects artificial devices and the brain. It can not only record neural signals, but also stimulate tissues. The recording electrode converts bioelectric signals into electrical signals that can be read by external devices. Although electrode technology has developed rapidly, it still faces many challenges: (1) biocompatibility challenges with brain tissue; (2) challenges in recording a large number of different types of neurons; (3) challenges in long-term reliable recording, etc. Since the 21st century, recording electrodes have made progress in many aspects. The size has become smaller and smaller, the number of channels has increased, the application of flexible materials has made flexible electrodes possible, the elastic coefficient has been lowered, multiplexing has been achieved, and the number of channels required for recording has been reduced. Microwire electrodes are the earliest electrodes used, mainly composed of fine metal wires. The electrode wire material can be stainless steel, tungsten, platinum / iridium and other materials. Generally, the diameter of the electrode wire is tens of microns. Except for the tip, the surface of the metal microwire is wrapped by an insulating layer such as acetyl imide several microns thick. The tip is the recording site.

[0003] The electrodes currently manufactured have low consistency, few channels, and general biocompatibility. Implantation into the brain usually produces an inflammatory response, which reduces the signal-to-noise ratio of the recorded signal. Therefore, electrophysiological recordings are in urgent need of a new type of implantable electrode with a high number of channels, a high signal-to-noise ratio, and high biocompatibility. Electrodes in the prior art cannot be reused for chronic implantation. Since existing electrodes can only record signals from the tip contacts, it is impossible to control the implantation of all electrode sites into the mitral cell layer, resulting in a lack of rich spatial information in the recorded signals, which is not conducive to studying the decoding of olfactory signals in rats.

[0004] The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known to a person of ordinary skill in the art. Summary of the invention

[0005] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a method for preparing a spatial electrode based on a focused ion beam and an electrode, which forms point-like exposures at different heights of each metal wire to form a two-in-one electrode for signal extraction and stimulation, and which is low-cost, high-performance implantable and reusable.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] A method for preparing a space electrode based on a focused ion beam of the present invention comprises:

[0008] Step 1, drawing a metal wire to form a plurality of electrode wires of a predetermined length and a predetermined diameter, wherein four electrode wires are grouped together and the tips of the four electrode wires are aligned, and then fixed to an electrode wire auxiliary device after being glued, rotated counterclockwise for multiple turns and then clockwise for multiple turns, and finally the front end is cut off evenly to form a thin wire;

[0009] Step 2, aligning multiple sets of insulating sleeves in a row and fixing them to the electrode bracket, multiple sets of filaments respectively pass through the multiple sets of insulating sleeves with their front ends flush, and the ends of the multiple sets of filaments are respectively connected to the connector interfaces and fixed with solder;

[0010] Step 3, using an electrostatic lens to focus the ion beam into a micro-cutting beam to punch holes in the filament, exposing a local cylindrical surface of the electrode wire as a contact point, and sealing the end of the wire with a photosensitive resin;

[0011] Step 4, fix the connector interface to the electrode bracket, insert multiple groups of punched filaments into the polyethylamide tube and fix the rear end, untwist the filaments near the connector interface, peel off the insulating sleeve layer, pass one end through the REF hole of the PCB board and weld it.

[0012] In the method, the metal wire comprises a tungsten wire or a nickel-chromium alloy wire, and the insulating sleeve is made of polyimide.

[0013] In the method described, the electrode support is formed by 3D printing using PEEK material.

[0014] In the method described, the connector interface is an Omnetics interface.

[0015] In the method described, a microcutting beam is used to punch holes in the filament to form square holes of 20*40 microns, the hole centers of the square holes are spaced 140 microns apart and the hole centers are kept in the same plane, the insulating sleeve is cut off through the opening to expose the local cylindrical surface of the electrode wire as a contact, and the ends of the filaments are sealed with a photosensitive resin.

[0016] In the method described, the connector interface is fixed to the electrode holder with screws, multiple groups of filaments are respectively inserted into the polyethylamide tube, and the rear end is fixed with 502 glue. Finally, the length is cut to ensure that the front ends are aligned, and the distance between the filaments is 200 microns. After the glue is cured, the filaments near the connector interface are untwisted, and the insulating sleeve is peeled off with tweezers to ensure that the insulating sleeve at the part where the filaments contact the pad has been peeled clean. The insulation layer of a section of silver wire is completely peeled off, one end is passed through the REF hole of the PCB board and welded, and the excess section is pulled off. The silver wire is used as a reference wire; one end of a silver wire is passed through the GND via of the PCB board and welded, and the excess part is pulled off. The silver wire is used as a ground wire.

[0017] A space electrode is manufactured by a space electrode manufacturing method based on a focused ion beam.

[0018] In the spatial electrode, the spatial electrode includes four electrodes, and the four electrodes constitute a micro-actuated microwire olfactory bulb cluster array electrode with a three-dimensional spatial arrangement.

[0019] Beneficial Effects

[0020] The present invention etches the specific parts of each electrode wire on the four electrodes, such as the insulating layer determined by the distribution position of the specific neurons of the olfactory bulb, to expose the metal layer to form point contacts, and the bottom cross-section of the four electrodes is insulated with a polyimide resin coating, which not only avoids the complex photolithography process of silicon-based materials, but also gives full play to the superior ductility of the metal wire, avoiding the drawbacks of the silicon-based materials being brittle and fragile. The two functions of signal extraction and stimulation can be realized on the same electrode in a time-sharing manner. In addition, since the existing electrodes can only record the signals of the tip contacts, it is impossible to control the electrode sites to be implanted in the mitral cell layer, so that the recorded signals lack rich spatial information, which is not conducive to studying the olfactory signal decoding of rats. The spatial electrode of the present invention can ensure that the electrode wires are implanted in the cell layer of interest with the help of the brain spectrum, thereby ensuring the richness and decodability of the signal.

[0021] The above description is only an overview of the technical solution of the present invention. In order to make the technical means of the present invention clearer and to enable those skilled in the art to implement it according to the contents of the specification, and to make the above and other purposes, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described below by way of example. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For ordinary technicians in this field, other drawings can also be obtained based on these drawings.

[0023] By reading the detailed description of the preferred specific embodiments below, various other advantages and benefits of the present invention will become clear to those of ordinary skill in the art. The drawings in the specification are only for the purpose of illustrating the preferred embodiments and are not considered to be limitations of the present invention. Obviously, the drawings described below are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative work. Moreover, the same reference numerals are used to represent the same components throughout the drawings.

[0024] In the attached picture:

[0025] Figure 1 It is a structural schematic diagram of a space electrode according to a method for preparing a space electrode based on a focused ion beam provided by the present invention;

[0026] Figure 2 It is a schematic diagram of photolithography drilling of electrode wire by a focused ion beam according to an embodiment of the present invention;

[0027] Figure 3 This is a schematic diagram of a 64-lead micro-actuated microwire olfactory bulb cluster array electrode provided by the present invention;

[0028] Figure 4 This is an image of a tetrode processed using a focused ion beam under a microscope;

[0029] Figure 5 It is a schematic diagram of the physical dimensions of the electrode under a microscope, and the unit length of the scale is mm;

[0030] Figure 6 This is a schematic diagram of the local field potential recorded after a 64-conductor electrode was implanted in the olfactory bulb of a rat.

[0031] The present invention is further explained below in conjunction with the accompanying drawings and embodiments. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, it does not require further definition and explanation in subsequent drawings.

[0035] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0036] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0037] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be directly connected or indirectly connected through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0038] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0039] In order to enable those skilled in the art to better understand the technical solution of the present invention, Figures 1 to 6 The present invention is further described in detail, and the accompanying drawings do not constitute a limitation on the embodiments of the present invention.

[0040] In one embodiment, if Figures 1 to 4 As shown, the present disclosure provides a method for preparing a space electrode based on a focused ion beam, comprising the following steps:

[0041] Step 1, drawing a metal wire to form a plurality of electrode wires of a predetermined length and a predetermined diameter, wherein four electrode wires are grouped together and the tips of the four electrode wires are aligned, and then fixed to an electrode wire auxiliary device after being glued, rotated counterclockwise for multiple turns and then clockwise for multiple turns, and finally the front end is cut off evenly to form a thin wire;

[0042] Step 2, aligning multiple sets of insulating sleeves in a row and fixing them to the electrode bracket, multiple sets of filaments respectively pass through the multiple sets of insulating sleeves with their front ends flush, and the ends of the multiple sets of filaments are respectively connected to the connector interfaces and fixed with solder;

[0043] Step 3, using an electrostatic lens to focus the ion beam into a micro-cutting beam to punch holes in the filament, exposing a local cylindrical surface of the electrode wire as a contact point, and sealing the end of the wire with a photosensitive resin;

[0044] Step 4, fix the connector interface to the electrode bracket, insert multiple groups of punched filaments into the polyethylamide tube and fix the rear end, untwist the filaments near the connector interface, peel off the insulating sleeve layer, pass one end through the REF hole of the PCB board and weld it.

[0045] In a preferred embodiment of the method, the metal wire includes tungsten wire or nickel-chromium alloy wire, and the insulating sleeve is made of polyimide. The metal wire is tungsten wire or nickel-chromium alloy wire. Compared with metal wires such as steel wire, these two materials are stable, corrosion-resistant, and high-strength at high temperatures, and can still maintain their strength in high temperature environments. Due to its stability and strength, it is usually used in the production of high-strength electrodes and complex-shaped electrodes, but the biocompatibility of tungsten wire is slightly poor, and it will damage the brain tissue of the subject during long-term implantation. In the preparation of biological invasive electrodes, the most suitable metal wire is platinum wire, which has good biocompatibility in addition to the advantages of other metal wires, but the disadvantage is that the cost is too high. In addition, silver wire is used as a reference wire and a ground wire. The insulating sleeve uses insulating materials such as polyimide. Polyimide is a high-performance engineering plastic with good high temperature resistance, chemical resistance and mechanical properties, and is widely used in aerospace, automotive, electronics and other fields. It has excellent mechanical properties, and its tensile strength is usually between 150-200+MPa and its yield strength is between 100-150+MPa. At the same time, polyimide has a higher elastic modulus and hardness, so that it has good anti-bending and compression performance. Polyimide material also has good chemical resistance, can resist the erosion and dissolution of various chemical substances, has good stability in common solvents such as acids and alkalis, is not prone to corrosion and dissolution, and is widely used in chemical processes and corrosive environments. Finally, polyimide material has excellent electrical properties, with high surface resistivity and volume resistivity. The insulation performance of polyimide is excellent, and it can maintain good insulation performance under high voltage, and is not prone to leakage and breakdown. The electrode interface is an Omnetics interface or a headstage interface, which is used to connect Tetrode to a data acquisition system. Among them, the headstage interface is preferably a headstage, which provides a series of analog and digital signal headstages to be suitable for different experimental types, such as acute and chronic experiments, large animals or small animal experiments, etc. In addition, according to the difference in the recorded signal, it is also divided into a high impedance headstage and a low impedance headstage. The present invention uses a high impedance headstage.

[0046] In a preferred embodiment of the method, the metal wire is drawn into a plurality of electrode wires with a diameter of 20 microns and a length of 1.1 cm by mechanical wire drawing.

[0047] In a preferred embodiment of the method, each group of four electrode wires is glued and fixed to an auxiliary device around the electrode wire, rotated counterclockwise for 25 times, then rotated clockwise for five times, and finally the front end is cut off flushly with a tungsten steel shear. In the method, a mechanical wire drawing process is used to draw the metal wire (the following content refers to tungsten wire, and the advantages and disadvantages of the metal wire have been described above) into a diameter of 20 microns; generally speaking, the diameter can be between 20 microns and 35 microns, but since the target electrode derivative of the present invention is 64 leads, the smaller the electrode wire diameter is within the range, the better, which helps to implant the target brain area during surgery and reduce damage to the target brain area of ​​the subject, thereby being more conducive to the long-term recording of electrode signals. The electrode wires that meet the diameter requirements are sorted and stored, and can be rolled into bundles or prepared into straight wires. The present invention selects the former.

[0048] Use tungsten steel scissors to cut the tungsten wire into 64 pieces with a length of about 11 cm, ensuring that the diameter and length of each filament are relatively consistent. This is to ensure that the final array is neat and consistent, but the length can be uniformly trimmed during the filament assembly process to make the front end flush. Divide the prepared electrode wires into groups of four, ensuring that the tips of the four electrode wires are aligned, and fix them to the spinner (wire winding auxiliary equipment) after gluing them with ordinary solid glue. Rotate counterclockwise for 25 times and then clockwise for five times. This is to reduce the tension of the electrode wire, making the wound front end straighter and harder. Finally, use tungsten steel scissors to cut off the front end flushly, and repeat the above steps to make sixteen groups.

[0049] In a preferred embodiment of the method, the electrode holder is formed by 3D printing using PEEK material.

[0050] In a preferred implementation of the method, the connector interface is an Omnetics interface.

[0051] In one embodiment,

[0052] Surface coating:

[0053] Wash the finished Tetrode to ensure a clean surface.

[0054] Carry out necessary packaging to protect the Tetrode.

[0055] Preparation of insulating sleeve and electrode holder:

[0056] Cut the insulating sleeve to the required length, process the insulating sleeve to ensure it is flat and smooth, and use 3D printing technology to make the electrode holder of PEEK material.

[0057] Filament Assembly:

[0058] The insulating sleeves are arranged in 4X4 groups and kept in the same plane. The row and column spacing is 200 microns. Align the insulating sleeves in a row and fix them to the electrode holder with 502 glue. Make sure that the insulating sleeves have a passage in front and back, otherwise the electrode wires will not be able to pass through. Under the microscope, use tweezers to pass the sixteen groups of wires through the insulating sleeves separately, so that they are isolated from each other but kept together.

[0059] Make sure there is enough length left on the end of the filament to connect to the Omnetics connector.

[0060] Make sure the front is flush

[0061] insulation:

[0062] Insulate the filaments with insulating sleeves to avoid short circuits between the filaments.

[0063] Connecting the Omnetics interface:

[0064] Under a microscope, holding tweezers, connect the ends of the 64 electrode wires to the Omnetics interface respectively, and fix them with solder. At this time, use tweezers to gently scrape off the insulation layer, and then use a welding gun to melt it. Pull the electrode wire slightly back under the microscope field of view so that the end of the electrode wire is connected to the interface through solder to ensure a firm connection.

[0065] In a preferred embodiment of the method, a microcutting beam is used to punch holes in the filament to form square holes of 20*40 microns, the center distance of the square holes is 140 microns and the hole centers are kept in the same plane, the holes are opened and the insulating sleeve is removed to expose the local cylindrical surface of the electrode wire as a contact, and the ends of the filaments are sealed with photosensitive resin.

[0066] In a preferred embodiment of the method, the connector interface is fixed to the electrode holder with screws, multiple groups of filaments are respectively inserted into the polyethylamide tube, and the rear end is fixed with 502 glue. Finally, the length is cut to ensure that the front ends are aligned, and the distance between the filaments is 200 microns. After the glue is cured, the filaments near the connector interface are untwisted, and the insulating sleeve is peeled off with tweezers to ensure that the insulating sleeve at the part where the filaments contact the pad has been peeled clean. The insulating layer of a section of silver wire is completely peeled off, one end is passed through the REF hole of the PCB board and welded, and the excess section is pulled off. The silver wire is used as a reference wire; one end of a silver wire is passed through the GND via of the PCB board and welded, and the excess part is pulled off. The silver wire is used as a ground wire.

[0067] In one embodiment, a method for preparing a spatial electrode based on a focused ion beam includes:

[0068] Materials preparation:

[0069] Metal wire: Tungsten wire or nickel-chromium alloy wire. Silver wire is used as reference wire and ground wire.

[0070] Insulating sleeve: Use insulating materials such as polyimide.

[0071] Omnetics interface: used to connect Tetrode to the data acquisition system.

[0072] Filament preparation:

[0073] Sixty-four wires were drawn using a mechanical wire drawing process into 20 micron diameter and 11 cm length.

[0074] Make sure each filament is relatively consistent in diameter and length.

[0075] Make a group of four electrode wires, ensure that the tips of the four electrode wires are aligned, glue them firmly and fix them to the spinner (wire winding auxiliary equipment), rotate them counterclockwise for 25 times, then rotate them clockwise for five times, and finally use tungsten steel shears to cut off the front end flushly, repeat the above steps to make sixteen groups.

[0076] Preparation of insulating sleeve and electrode holder:

[0077] Cut the insulating sleeve to the required length, process the insulating sleeve to ensure it is flat and smooth, and use 3D printing technology to make the electrode holder of PEEK material.

[0078] Filament Assembly:

[0079] The insulating sleeves are in 4X4 groups, and they are kept in the same plane. Align the insulating sleeves in a row and fix them to the electrode holder with 502 glue. Make sure that the insulating sleeves have front and back passages, otherwise the electrode wires will not be able to pass through. Under a microscope, use tweezers to pass the sixteen groups of wires through the insulating sleeves separately, isolating them from each other but keeping them together.

[0080] Make sure there is enough length left on the end of the filament to connect to the Omnetics connector.

[0081] Make sure the front is flush

[0082] insulation:

[0083] Insulate the filaments with insulating sleeves to avoid short circuits between the filaments.

[0084] Connecting the Omnetics interface:

[0085] Under a microscope, holding tweezers, connect the ends of the 64 electrode wires to the Omnetics interface respectively, and fix them with solder. At this time, use tweezers to gently scrape off the insulation layer, and then use a welding gun to melt it. Pull the electrode wire slightly back under the microscope field of view so that the end of the electrode wire is connected to the interface through solder to ensure a firm connection.

[0086] Testing and debugging:

[0087] Test the electrical properties of each filament to ensure that the resistance and conductivity meet the requirements.

[0088] You can use a microscope or other tools to check the appearance and connection of the Tetrode.

[0089] Fib Technology:

[0090] Focused ion beam (FIB) is a microdissection technique that uses an electrostatic lens to focus an ion beam into a very small size. Further, the particle beam is drawn from a liquid metal ion source. In the present invention, the prepared tetrode is punched using the FIB technique.

[0091] Specifically, the hole is a square hole, 20*40 microns, with a hole center distance of 140 microns. The hole center basically maintains a plane. The polyimide resin coating is cut off to expose the local cylindrical surface of the electrode wire as a contact. The end of the wire is sealed with a photosensitive resin.

[0092] Surface coating:

[0093] Wash the finished Tetrode to ensure a clean surface.

[0094] Carry out necessary packaging to protect the Tetrode.

[0095] Then comes the electrode manufacturing process:

[0096] Use M3 screws to fix the omnetics interface to the prepared electrode holder, insert the sixteen groups of prepared tetrodes into the polyimide tube, and fix the rear end with 502 glue. Finally, cut the length to ensure that the front end is aligned, and the distance between the electrode wires is about 200 microns. After the glue solidifies, untwist the electrode wire near the interface, and use tweezers to peel off a section of the insulation layer; ensure that the insulation layer of the part where the electrode wire contacts the pad has been stripped clean. Strip off the insulation layer of a section of silver wire, pass one end through the REF hole of the PCB board and weld it, pull off the excess section, and use this silver wire as a reference wire; pass one end of a silver wire through the GND via of the PCB board and weld it, pull off the excess part, and use this silver wire as a ground wire. Furthermore, the silver wire is 50 microns in diameter, and two sections of silver wire with a length of about 5 cm are directly cut to be used as a reference wire and a ground wire respectively.

[0097] A space electrode is manufactured by a space electrode manufacturing method based on a focused ion beam.

[0098] In one embodiment, the spatial electrode includes four electrodes, and the four electrodes constitute a micro-actuated micro-wire olfactory bulb cluster array electrode with a three-dimensional spatial arrangement. The present invention utilizes a focused ion beam to process electrodes, so that point-like exposure can be formed at different heights of each metal wire to form a two-in-one electrode for signal extraction and stimulation. Titanium wire has superior performance and good biocompatibility, and can be used as both a sensing electrode and a stimulation electrode. The electrochemical damage to nerves is minimal. The 64-lead micro-actuated micro-wire olfactory bulb cluster array electrode with a three-dimensional spatial arrangement etches the insulating layer of each electrode wire on the four electrodes according to the distribution position of the specific neurons of the olfactory bulb, exposes the metal layer to form point contacts, and the bottom cross-section of the four electrodes is insulated with a polyimide resin (photosensitive resin), and finally developed into a 64-lead micro-actuated micro-wire olfactory bulb cluster array electrode that can match and record the distribution of neurons of interest in the olfactory bulb (such as mitral cells). The 64-lead three-dimensional high-stability rat olfactory bulb cluster array electrode is a three-dimensional structure, forming a 4X4 cluster electrode array in a 1mm X 1mm X 1mm space. Each cluster electrode contains 4 titanium wires with a thickness of 12.5μm and a height difference of 160μm and a polyimide resin coating. The tip of the wire is exposed to form an electrode. Due to the superior performance and good biocompatibility of titanium wire, it can be used as both a sensing electrode and a stimulation electrode. The electrochemical damage to the nerve is minimal. Therefore, the electrode array to be developed in this project can not only avoid the complex photolithography process of silicon-based materials, but also give full play to the superior ductility of the metal wire, avoiding the disadvantages of the brittleness and fragility of silicon-based materials. And the two functions of signal extraction and stimulation can be realized on the same electrode in a time-sharing manner. Since the existing electrodes can only record the signals of the tip contacts, it is impossible to control the implantation of all the electrode sites into the mitral cell layer, so that the recorded signals lack rich spatial information, which is not conducive to the study of olfactory signal decoding in rats. The spatial electrode produced by the present invention can ensure that the electrode wires are implanted into the cell layer of interest with the help of brain spectrogram, thereby ensuring the richness and decodability of the signal.

[0099] In one embodiment, the rat olfactory bulb cluster array electrode of the present invention adopts a three-dimensional structure to form a cluster electrode in space, and each cluster electrode contains 4 titanium wires / tungsten wires with different heights of 12.5 μm and coated with polyimide resin. The tips of the wires are exposed to form a two-in-one electrode for signal extraction and stimulation. The advantages of silicon probes that can record neuronal activities at different depths and microwire olfactory bulb cluster array electrodes that can record neuronal activities over a large area are combined, and four electrodes (tetrodes) are combined to form a 64-lead microwire olfactory bulb cluster array electrode that can be micro-driven with a three-dimensional spatial arrangement.

[0100] In one embodiment, testing and debugging:

[0101] Appearance quality inspection

[0102] Electrode volume inspection: Check whether the volume of the tested electrode meets the invention objectives

[0103] See also Figure 5 , visually inspect the number of electrode wires of the 64-conductor electrode under a microscope to see if it is 4×4×4 conductors; visually inspect the physical size of the 64-conductor electrode under a microscope to see if it is 1 mm×1 mm×1 mm

[0104] Check the arrangement size of the electrode contacts in the space array: Test the arrangement size of the electrode contacts in the space array

[0105] During the inspection, the diameter of the electrode bundle is measured by taking a photo in the axial direction of the electrode using a tool optical microscope (with a large depth of field) that is strictly calibrated with a length measuring tool that meets national standards. After the electrode is rotated along the axial direction as a whole, the diameters in the three directions of length, width and height are recorded. The diameters of the electrode bundle in the three directions are all less than 1mm. In the three directions recorded, all the contacts are along the axial direction of the electrode bundle, and the distance between each other is less than Lx. During the test, the distance between the contact farthest from the end of the electrode bundle and the contact closest to it can be measured.

[0106] Weight parameter check

[0107] Check whether the weight of the tested electrode is less than 5g. First calibrate the electronic balance to zero, weigh the 64-conductivity electrode, and check whether it meets the requirements. After testing, the weight of the current samples is between 0.9g and 1g, which meets the target requirements.

[0108] Collection performance check

[0109] Check whether the field potential can be collected by the test electrode.

[0110] Healthy SD rats were selected for electrode implantation surgery. According to the standard rat brain atlas, the implantation range of the electrodes was determined, i.e. 7.28mm forward from bregma, 1.0mm on the right side, and 2.5-3.5mm in depth. A 64-lead cluster array electrode was implanted in the right olfactory bulb of the rat using a stereotaxic device. The electrodes were fixed on the rat skull using dental cement and the field potential signals were tested after the rats recovered. The rats were anesthetized first, and the electrodes were connected to a 32-channel in vivo multi-channel neural signal acquisition system (Cerebus) to collect the field potential signals and examine them.

[0111] Ensure that after the 64-lead electrode is implanted in the olfactory bulb, each lead can record a stable local field potential, see Figure 6 .

[0112] Electrical connection test.

[0113] To test the electrical connection characteristics of the electrode, follow these steps:

[0114] Take a piece of agar with the same size of 50mm×50mm×50mm as the conductivity of biological tissue and set aside;

[0115] Take two pieces of 10mm×20mm×0.2mm medical 304 stainless steel metal sheets for use;

[0116] Insert two metal sheets into the agar in parallel and at equal depths with a spacing of 10 mm along the length direction, with 10 mm exposed on each sheet.

[0117] Use alligator clips to connect the metal sheets to the positive and negative output terminals of the low-frequency signal generator respectively;

[0118] Set the low-frequency signal generator to output a 1KHz, 100mV sinusoidal voltage signal;

[0119] Gently insert the 64-channel electrode into the middle of the two metal sheets of agar, at an equal distance from the two metal sheets;

[0120] Connect the dual-channel oscilloscope channel 1 input to the low-frequency signal generator output, and the channel 2 input to the 64-channel electrode connector;

[0121] Measure the analog voltage signal detected by each channel of the 64 channels from the 64-channel electrode connector;

[0122] Qualified judgment: If the waveform displayed on each channel is in the same phase as the waveform output by the signal generator, the amplitude is about 50mV, and the signal amplitude of each channel is different, and the fluctuation range is between 2.5mV and 10mV, the electrical connection of the channel is judged to be qualified. If there is no signal or the amplitude of the waveform displayed on adjacent channels is completely consistent (the amplitude difference is less than 0.5mV), the electrical connection of the channel is judged to be unqualified. Ensure that each of the 64 leads is qualified.

[0123] Although the embodiments of the present invention are described above in conjunction with the accompanying drawings, the present invention is not limited to the above specific embodiments and application fields, and the above specific embodiments are only illustrative and instructive, rather than restrictive. A person of ordinary skill in the art can also make many forms under the guidance of this specification and without departing from the scope of protection of the claims of the present invention, all of which belong to the protection of the present invention.

Claims

1. A method for preparing a space electrode based on a focused ion beam, characterized in that: It includes the following steps: Step 1, drawing a metal wire to form a plurality of electrode wires of a predetermined length and a predetermined diameter, wherein four electrode wires are grouped together and the tips of the four electrode wires are aligned, and then fixed to an electrode wire auxiliary device after being glued, rotated counterclockwise for multiple turns and then clockwise for multiple turns, and finally the front end is cut off evenly to form a thin wire; Step 2, aligning multiple sets of insulating sleeves in a row and fixing them to the electrode bracket, multiple sets of filaments respectively pass through the multiple sets of insulating sleeves with their front ends flush, and the ends of the multiple sets of filaments are respectively connected to the connector interfaces and fixed with solder; Step 3, using an electrostatic lens to focus the ion beam into a micro-cutting beam to punch holes in the filament, exposing a local cylindrical surface of the electrode wire as a contact point, and sealing the end of the wire with a photosensitive resin; Step 4, fix the connector interface to the electrode bracket, insert multiple groups of punched filaments into the polyethylamide tube and fix the rear end, untwist the filaments near the connector interface, peel off the insulating sleeve layer, pass one end through the REF hole of the PCB board and weld it.

2. The method according to claim 1, characterized in that Preferably, the metal wire comprises a tungsten wire or a nickel-chromium alloy wire, and the insulating sleeve is made of polyimide.

3. The method according to claim 1, characterized in that: The metal wire was drawn into a plurality of electrode wires with a diameter of 20 microns and a length of 11 cm using mechanical wire drawing.

4. The method according to claim 1, characterized in that Each group of four electrode wires is glued and fixed to the electrode wire auxiliary equipment, which is rotated counterclockwise for 25 circles, then clockwise for five circles, and finally the front end is cut off flushly with tungsten steel shears.

5. The method according to claim 1, characterized in that The electrode holder is formed by 3D printing using PEEK material.

6. The method according to claim 1, characterized in that The connector interface is an Omnetics interface.

7. The method according to claim 1, characterized in that The microcutting beam punches holes in the filament to form square holes of 20*40 microns. The center distance of the square holes is 140 microns and the hole centers are kept in the same plane. The insulating sleeve is removed through the opening to expose the local cylindrical surface of the electrode wire as a contact, and the end of the filament is sealed with photosensitive resin.

8. A space electrode, characterized in that: The spatial electrode is manufactured by the method for preparing the spatial electrode based on a focused ion beam according to any one of claims 1 to 7.

9. The space electrode according to claim 8, characterized in that: The spatial electrode comprises four electrodes, and the four electrodes constitute a microwire olfactory bulb cluster array electrode with a three-dimensional spatial arrangement and micro-actuation.

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