Focused ion beam based method for spatial electrode fabrication and electrode
The space electrode fabricated by focused ion beam solves the problems of low uniformity, low channel number and poor biocompatibility of existing electrodes, realizes high channel number and reusable electrode, improves signal richness and decoding capability, and enhances biocompatibility.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-04-18
- Publication Date
- 2026-03-31
AI Technical Summary
Existing brain-computer interface electrodes suffer from problems such as low consistency, limited number of channels, poor biocompatibility, low signal-to-noise ratio, and inability to be reused when implanted into brain tissue. This results in a lack of rich spatial information in the recorded signals, making it difficult to effectively decode rat olfactory signals.
A spatial electrode was fabricated using a focused ion beam method. By forming point-like exposed contacts at different heights on each metal wire, combined with a polyimide insulating layer and an Omnetics interface, an electrode combining signal extraction and stimulation was formed. A three-dimensionally arranged microfilament olfactory bulb cluster array electrode was used to ensure that the electrode wires were implanted into the cell layer of interest.
This invention enables high-channel-count, low-cost, and reusable electrodes, improving signal richness and decodeability, reducing damage to brain tissue, and enhancing biocompatibility.
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Figure CN119564217B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of power system operation and dispatch automation technology, and in particular to a method for preparing a space electrode based on a focused ion beam. Background Technology
[0002] Brain-computer interface (BCI) technology bridges the communication gap between the brain and artificial devices. A crucial role of BCI is deciphering brain information, using animals with special sensory abilities as biosensors. By deciphering the neurophysiological signals of the relevant sensory cortex, useful information can be extracted. For example, decoding the electrophysiological signals in the olfactory or gustatory systems of rodents can detect very low concentrations of chemical substances. Odor detection plays an important role in social security and prevention, such as food safety control, environmental monitoring, drug detection, and explosives detection. Recording electrodes in BCI are key components connecting artificial devices and the brain. They can record neural signals and also be used to stimulate tissues. Recording electrodes convert bioelectrical signals into electrical signals that can be read by external devices. Despite the rapid development of electrode technology, several challenges remain: (1) the challenge of biocompatibility with brain tissue; (2) the challenge of recording a large number of different types of neurons; and (3) the challenge of reliable recording over long periods. Since the 21st century, recording electrodes have made progress in many aspects, becoming smaller and smaller, with an increased number of channels. The application of flexible materials has made flexible electrodes possible, with lower elastic coefficients, enabling multiplexing and reducing the number of channels required for recording. Microwire electrodes were the earliest type of electrode used, primarily composed of fine metal wires. The electrode wires can be made of materials such as stainless steel, tungsten, or platinum / iridium. Typically, the diameter of the electrode wire is tens of micrometers. Except for the tip, the surface of the metal microwire is covered by an insulating layer of several micrometers thick, such as acetylimine. The tip serves as the recording site.
[0003] Current electrodes exhibit low consistency, limited channel count, and generally poor biocompatibility. Implantation in the brain often induces inflammation, reducing the signal-to-noise ratio (SNR) of the recorded signal. Therefore, electrophysiological recording urgently requires a novel implantable electrode with high channel count, high SNR, and high biocompatibility. Existing electrodes are not reusable for chronic implantation. Because current electrodes can only record signals from the tip contact point and cannot control the implantation of the electrode site to the mitral cell layer, the recorded signals lack rich spatial information, which is detrimental to studies such as decoding olfactory signals in rats.
[0004] The information disclosed in the background section is only intended to enhance the understanding of the background of the present invention, and therefore may contain information that does not constitute prior art known to those skilled in the art. Summary of the Invention
[0005] To address the shortcomings of existing technologies, the present invention aims to provide a method and electrode for preparing a spatial electrode based on a focused ion beam. This method creates point-like exposures at different heights on each metal wire, forming a dual-purpose electrode for signal extraction and stimulation. The electrode is low-cost, high-performance, and reusable.
[0006] To achieve the above objectives, the present invention provides the following technical solution:
[0007] A method for fabricating a space electrode based on a focused ion beam according to the present invention includes:
[0008] Step 1: Draw the metal wire into multiple electrode wires of predetermined length and diameter. Set up groups of four electrode wires with the tips of the four electrode wires aligned. Secure them with glue and then fix them to the electrode wire winding auxiliary equipment. Rotate counterclockwise multiple times and then clockwise multiple times. Finally, cut off the front end evenly to form a thin wire.
[0009] Step 2: Multiple sets of insulating sleeves are aligned and arranged in a row and fixed to the electrode support. Multiple sets of filaments pass through multiple sets of insulating sleeves with their front ends flush. The ends of the multiple sets of filaments are connected to the connector interface and fixed with solder.
[0010] Step 3: Use an electrostatic lens to focus the ion beam into a micro-cutting beam to drill holes in the filament, exposing a local cylindrical surface of the electrode wire as a contact point, and seal the end of the filament with photosensitive resin.
[0011] Step 4: Fix the connector interface to the electrode bracket, thread multiple sets of perforated filaments into the polyamide tube and fix the rear end, unwind the filament near the connector interface, peel off the insulating sleeve layer, and thread one end through the REF hole of the PCB board and solder it.
[0012] In the method described, the metal wire includes tungsten wire or nickel-chromium alloy wire, and the insulating sleeve is made of polyimide.
[0013] In the method described, the electrode holder 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, the micro-cutting beam punches holes in the filament to form 20*40 micrometer square holes. The center-to-center distance of the square holes is 140 micrometers and the center of the holes is kept on the same plane. The insulating sleeve is cut through the hole to expose a local cylindrical surface of the electrode wire as a contact point. The end of the filament is sealed with photosensitive resin.
[0016] In the method described, screws are used to fix the connector interface to the electrode bracket. Multiple sets of filaments are threaded into polyamide tubes and fixed at the rear end with 502 glue. Finally, the length is cut to ensure that the front ends are aligned. The distance between the filaments is 200 micrometers. After the glue cures, the filament near the connector interface is unscrewed, and the insulating sleeve is peeled off with tweezers to ensure that the insulating sleeve at the part of the filament that contacts the solder pad has been completely removed. The insulation layer of a section of silver wire is completely removed, one end is passed through the REF hole of the PCB board and soldered, and the excess section is pulled off. This silver wire serves as a reference wire. One end of a silver wire is passed through the GND via of the PCB board and soldered, and the excess section is pulled off. This silver wire serves as a ground wire.
[0017] A space electrode is fabricated via a space electrode fabrication method based on a focused ion beam.
[0018] The space electrode includes four electrodes, which together form a micro-drivable microfilament olfactory sphere cluster array electrode with a three-dimensional spatial arrangement.
[0019] Beneficial effects
[0020] This invention involves etching the insulating layer at specific locations on each electrode wire of the four electrodes, such as the distribution of specific neurons in the olfactory bulb, to expose the metal layer and form dotted contacts. The bottom cross-section of the four electrodes is insulated with a polyimide resin coating. This not only avoids the complex photolithography process of silicon-based materials but also fully utilizes the superior ductility of metal wires, avoiding the brittleness and fragility of silicon-based materials. Furthermore, it allows for time-division multiplexing of signal extraction and stimulation functions on the same electrode. In addition, existing electrodes can only record signals from the tip contacts, making it impossible to control the implantation of all electrode sites into layers such as the mitral cell layer, resulting in a lack of rich spatial information in the recorded signals, which is detrimental to the decoding of olfactory signals in rats. The spatial electrode of this invention, with the aid of brain mapping, ensures that the electrode wires are implanted into the cell layer of interest, thereby guaranteeing signal richness and decodeability.
[0021] The above description is merely an overview of the technical solution of the present invention. In order to make the technical means of the present invention clearer and more understandable, so that those skilled in the art can implement it according to the contents of the specification, and in order to make the above and other objects, features and advantages of the present invention more obvious and understandable, specific embodiments of the present invention are described below. Attached Figure Description
[0022] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this invention. For those skilled in the art, other drawings can be obtained based on these drawings.
[0023] Various other advantages and benefits of the present invention will become apparent to those skilled in the art upon reading the detailed description of the preferred embodiments below. The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. It is obvious that the drawings described below are merely some embodiments of the invention, and those skilled in the art can obtain other drawings based on these drawings without any inventive effort. Furthermore, the same reference numerals denote the same parts throughout the drawings.
[0024] In the attached diagram:
[0025] Figure 1 This is a schematic diagram of the structure of a space electrode based on a focused ion beam space electrode fabrication method provided by the present invention;
[0026] Figure 2 This is a schematic diagram of a focused ion beam photolithography drilling of an electrode wire according to an embodiment of the present invention;
[0027] Figure 3 This is a schematic diagram of a 64-channel micro-driven microfilament olfactory ball cluster array electrode provided by the present invention;
[0028] Figure 4 These are images of Tetrode processed using a focused ion beam under a microscope;
[0029] Figure 5 This is a schematic diagram of the physical dimensions of the electrodes under a microscope. 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-conductive electrode was implanted into the olfactory bulb of a rat.
[0031] The present invention will be further explained below with reference to the accompanying drawings and embodiments. Detailed Implementation
[0032] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0033] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.
[0034] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.
[0035] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," and "counterclockwise," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.
[0036] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.
[0037] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.
[0038] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.
[0039] To enable those skilled in the art to better understand the technical solution of the present invention, the following will be described in conjunction with the appendix. Figures 1 to 6 The present invention will be described in further detail below, and the accompanying drawings are not intended to limit the embodiments of the present invention.
[0040] In one embodiment, such as Figures 1 to 4 As shown, this disclosure provides a method for fabricating a space electrode based on a focused ion beam, comprising the following steps:
[0041] Step 1: Draw the metal wire into multiple electrode wires of predetermined length and diameter. Set up groups of four electrode wires with the tips of the four electrode wires aligned. Secure them with glue and then fix them to the electrode wire winding auxiliary equipment. Rotate counterclockwise multiple times and then clockwise multiple times. Finally, cut off the front end evenly to form a thin wire.
[0042] Step 2: Multiple sets of insulating sleeves are aligned and arranged in a row and fixed to the electrode support. Multiple sets of filaments pass through multiple sets of insulating sleeves with their front ends flush. The ends of the multiple sets of filaments are connected to the connector interface and fixed with solder.
[0043] Step 3: Use an electrostatic lens to focus the ion beam into a micro-cutting beam to drill holes in the filament, exposing a local cylindrical surface of the electrode wire as a contact point, and seal the end of the filament with photosensitive resin.
[0044] Step 4: Fix the connector interface to the electrode bracket, thread multiple sets of perforated filaments into the polyamide tube and fix the rear end, unwind the filament near the connector interface, peel off the insulating sleeve layer, and thread one end through the REF hole of the PCB board and solder it.
[0045] In a preferred embodiment of the method, the metal wire comprises 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 to metal wires such as steel wire, these two materials exhibit stability, corrosion resistance, and high strength at high temperatures, maintaining their strength even in high-temperature environments. Due to their stability and strength, they are commonly used in the fabrication of high-strength electrodes and electrodes with complex shapes. However, tungsten wire has slightly poor biocompatibility and can damage the brain tissue of the test subject during prolonged implantation. Platinum wire is the most suitable metal wire for preparing bioinvasive electrodes, offering good biocompatibility in addition to the advantages of other metal wires, but its high cost is a drawback. Silver wire is used as a reference line and 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, and electronics fields. It possesses excellent mechanical properties, with tensile strength typically between 150-200+ MPa and yield strength between 100-150+ MPa. Meanwhile, polyimide possesses high elastic modulus and hardness, resulting in excellent bending and compressive strength. Polyimide materials also exhibit good chemical resistance, resisting the erosion and dissolution of various chemicals. They demonstrate good stability in common solvents such as acids and alkalis, and are not easily corroded or dissolved, making them widely used in chemical processes and corrosive environments. Finally, polyimide materials possess excellent electrical properties, exhibiting high surface and volume resistivity. Polyimide also has excellent insulation properties, maintaining good insulation performance under high voltage and being less prone to leakage and breakdown. The electrode interface is either an omnetics interface or a headstage interface, used to connect the Tetrode to the data acquisition system. A headstage interface is preferred, providing a range of analog and digital signal headstages suitable for different experimental types, such as acute and chronic experiments, large animal or small animal experiments, etc. Furthermore, depending on the recorded signal, headstages are also categorized as high-impedance and low-impedance. This invention uses a high-impedance headstage.
[0046] In a preferred embodiment of the method, a metal wire is drawn mechanically into multiple electrode wires with a diameter of 20 micrometers and a length of 11 cm.
[0047] In a preferred embodiment of the method, four electrode wires are glued together and fixed to an electrode wire auxiliary device, then rotated counterclockwise 25 times, then clockwise 5 times, and finally the front end is cut off evenly with tungsten carbide shears. In the method, a mechanical drawing process is used to draw the metal wire (hereinafter referring to tungsten wire; the advantages and disadvantages of metal wire have been described above) to a diameter of 20 micrometers. Generally, a diameter between 20 and 35 micrometers is acceptable, but since the target electrode of this invention has a conductance of 64, the smaller the electrode wire diameter within this range, the better. This facilitates surgical implantation into the target brain region and reduces damage to the target brain region of the subject, thus being more conducive to long-term recording of electrode signals. Electrode wires with the required diameter are organized and stored; they can be rolled into bundles or prepared as straight wires. This invention chooses the former.
[0048] Cut the tungsten wire into 64 pieces using tungsten carbide shears, each approximately 11cm long, ensuring that the diameter and length of each wire are relatively consistent. This is to ensure a neat and uniform final array, but the length can be further trimmed during wire assembly to ensure the front ends are aligned. Divide the prepared electrode wires into groups of four, ensuring the tips of the four electrode wires are aligned. Secure them to the spinner (an electrode wire winding aid) with ordinary solid glue, and rotate them counterclockwise 25 times, then clockwise 5 times. This is to reduce the tension of the electrode wire, making the wound front end straighter and harder. Finally, use tungsten carbide shears to cut off the front end evenly. Repeat the above steps to make sixteen groups.
[0049] In a preferred embodiment of the method, the electrode holder is formed using 3D printing via PEEK material.
[0050] In a preferred embodiment of the method, the connector interface is an Omnetics interface.
[0051] In one embodiment,
[0052] Surface coating:
[0053] Clean the finished Tetrode to ensure the surface is clean.
[0054] Properly package the Tetrode to protect it.
[0055] Preparation of insulating sleeve and electrode support:
[0056] The insulating sleeve is cut to the required length and processed to ensure its flatness and smoothness. Electrode supports are fabricated from PEEK material using 3D printing technology.
[0057] Wire assembly:
[0058] The insulating sleeves are arranged in 4x4 groups, keeping them on the same plane. The row and column spacing is 200 micrometers. The insulating sleeves are aligned in a row and fixed to the electrode holder with 502 glue, ensuring that the insulating sleeves remain open at both ends; otherwise, the electrode wires will not be able to pass through. Under the microscope, using tweezers, the sixteen groups of wires are threaded through the insulating sleeves one by one, isolating them from each other but keeping them together.
[0059] Ensure that the filament end has sufficient length for connection to the Omnetics interface.
[0060] Ensure front end is aligned
[0061] insulation:
[0062] Insulating sleeves are used to insulate the filaments to prevent short circuits between them.
[0063] Connect to the Omnetics interface:
[0064] Under the microscope, using tweezers, connect the ends of the 64 electrode wires to the Omnetics interface, and secure them with solder after passing them through. Then, gently scrape off the insulation layer with the tweezers and melt it with a soldering gun. Under the microscope, pull the electrode wires slightly backward so that the ends of the electrode wires are connected to the interface with solder, ensuring a firm connection.
[0065] In a preferred embodiment of the method, the micro-cutting beam punches holes in the filament to form 20*40 micrometer square holes. The center-to-center distance of the square holes is 140 micrometers and the centers of the holes are kept on the same plane. The insulating sleeve is cut through the holes to expose a partial cylindrical surface of the electrode wire as a contact point. The end of the filament is sealed with photosensitive resin.
[0066] In a preferred embodiment of the method, screws are used to fix the connector interface to the electrode bracket. Multiple sets of filaments are threaded into polyamide tubes and fixed at the rear end with 502 glue. Finally, the length is cut to ensure that the front ends are aligned. The distance between the filaments is 200 micrometers. After the glue cures, the filament near the connector interface is unscrewed, and the insulating sleeve is peeled off with tweezers to ensure that the insulating sleeve at the part of the filament in contact with the solder pad has been completely removed. The insulation layer of a section of silver wire is completely removed, one end is passed through the REF hole of the PCB board and soldered, and the excess section is pulled off. This silver wire serves as a reference wire. One end of a silver wire is passed through the GND via of the PCB board and soldered, and the excess part is pulled off. This silver wire serves as a ground wire.
[0067] In one embodiment, a method for fabricating a space 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 a reference line and ground wire.
[0070] Insulating sleeve: Made of insulating materials such as polyimide.
[0071] Omnetics interface: Used to connect Tetrode to the data acquisition system.
[0072] Filament preparation:
[0073] The metal wire was drawn into sixty-four strands with a diameter of 20 micrometers and a length of 11 cm using a mechanical drawing process.
[0074] Ensure that the diameter and length of each filament are relatively consistent.
[0075] Take four electrode wires as a group, ensuring the tips of the four electrode wires are aligned. Glue them firmly to the spinner (an auxiliary device for winding electrode wires), rotate counterclockwise 25 times, then clockwise 5 times. Finally, use tungsten carbide shears to cut off the front end evenly. Repeat the above steps to make sixteen groups.
[0076] Preparation of insulating sleeve and electrode support:
[0077] The insulating sleeve is cut to the required length and processed to ensure its flatness and smoothness. Electrode supports are fabricated from PEEK material using 3D printing technology.
[0078] Wire assembly:
[0079] The insulating sleeves are arranged in 4x4 groups, kept in the same plane. Align the insulating sleeves in a row and fix them to the electrode holder using 502 glue. Ensure that the insulating sleeves are unobstructed from front to back; otherwise, the electrode wires will not be able to pass through. Under the microscope, use tweezers to thread the sixteen groups of wires through the insulating sleeves one by one, isolating them from each other but keeping them together.
[0080] Ensure that the filament end has sufficient length for connection to the Omnetics interface.
[0081] Ensure front end is aligned
[0082] insulation:
[0083] Insulating sleeves are used to insulate the filaments to prevent short circuits between them.
[0084] Connect to the Omnetics interface:
[0085] Under the microscope, using tweezers, connect the ends of the 64 electrode wires to the Omnetics interface, and secure them with solder after passing them through. Then, gently scrape off the insulation layer with the tweezers and melt it with a soldering gun. Under the microscope, pull the electrode wires slightly backward so that the ends of the electrode wires are connected to the interface with solder, ensuring 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] The appearance and connections of the Tetrode can be examined using tools such as a microscope.
[0089] Fib technology:
[0090] Focused ion beam (FIB) is a micro-cutting technique that uses an electrostatic lens to focus an ion beam into a very small size. Furthermore, the particle beam is extracted from a liquid metal ion source. In this invention, FIB technology is used to drill holes in the prepared tetrade.
[0091] Specifically, the holes are square, 20*40 micrometers in size, with a center-to-center spacing of 140 micrometers. The center of each hole is essentially on a plane. The polyimide resin coating is removed through the openings, exposing the cylindrical surfaces of the electrode wires as contacts. The ends of the wires are sealed with photosensitive resin.
[0092] Surface coating:
[0093] Clean the finished Tetrode to ensure the surface is clean.
[0094] Properly package the Tetrode to protect it.
[0095] Next is the electrode manufacturing process:
[0096] Using M3 screws, secure the omnetics interface to the prepared electrode holder. Insert sixteen sets of prepared electrodes into polyethylene terephthalate tubes and secure the rear ends with 502 glue. Trim the wires to ensure alignment at the front ends, with a distance of approximately 200 micrometers between the electrode wires. After the glue cures, unscrew the electrode wire near the interface and use tweezers to peel off a section of insulation, ensuring the insulation is completely removed from the area where the electrode wire contacts the pad. Remove all insulation from a section of silver wire, thread one end through the REF hole on the PCB and solder it, then break off the excess; this silver wire serves as the reference wire. Thread one end of another silver wire through the GND via on the PCB and solder it, then break off the excess; this silver wire serves as the ground wire. Further, the silver wire is 50 micrometers in diameter; cut two sections approximately 5 cm long directly for use as the reference and ground wires, respectively.
[0097] A space electrode is fabricated via a space electrode fabrication method based on a focused ion beam.
[0098] In one embodiment, the spatial electrode comprises four electrodes, which constitute a micro-dervescent microfilament olfactory bulb cluster array electrode with a three-dimensional spatial arrangement. This invention utilizes focused ion beam processing to create point-like exposures at different heights on each metal wire, forming a dual-function electrode for signal extraction and stimulation. Titanium wire exhibits superior performance and good biocompatibility, serving as both a sensing and stimulating electrode. It causes minimal electrochemical damage to nerves. The 64-channel micro-dervescent microfilament olfactory bulb cluster array electrode with a three-dimensional spatial arrangement involves etching the insulating layer at specific locations on each of the four electrode wires, depending on the distribution of specific neurons in the olfactory bulb, exposing the metal layer to form point-like contacts. The bottom cross-section of the four electrodes is insulated with polyimide resin (photosensitive resin), ultimately creating a 64-channel micro-dervescent microfilament olfactory bulb cluster array electrode capable of matching and recording the distribution of neurons of interest (e.g., mitral cells) in the olfactory bulb. The 64-channel three-dimensional high-stability rat olfactory bulb cluster array electrode features a three-dimensional structure, forming a 4x4 cluster electrode array within a 1mm x 1mm x 1mm space. Each cluster electrode contains four 12.5μm thick titanium wires with a height difference of 160μm, coated with polyimide resin. The wire tips are exposed to form the electrodes. Due to the superior performance and good biocompatibility of titanium wires, they can be used as both sensing and stimulating electrodes, causing minimal electrochemical damage to nerves. Therefore, the electrode array to be developed in this project not only avoids the complex photolithography process of silicon-based materials but also fully utilizes the superior ductility of titanium wires, avoiding the brittleness and fragility of silicon-based materials. Furthermore, it can achieve both signal extraction and stimulation functions on the same electrode in a time-division manner. Because existing electrodes can only record signals from the tip contact points and cannot control the implantation of all electrode sites into the mitral cell layer, the recorded signals lack rich spatial information, which is detrimental to the decoding of rat olfactory signals. The spatial electrodes fabricated by this invention can ensure that the electrode wires are implanted into the cell layer of interest with the help of brain spectroscopy, thereby ensuring the richness and decodeability of the signal.
[0099] In one embodiment, the rat olfactory bulb cluster array electrode of the present invention adopts a three-dimensional structure, forming cluster electrodes in space. Each cluster electrode contains four titanium / tungsten wires with polyimide resin coatings, each 12.5 μm in height. The tips of the wires are exposed, forming a signal extraction and stimulation dual-function electrode. This combination leverages the advantages of silicon probes (capable of recording neuronal activity at different depths) and microfilament olfactory bulb cluster array electrodes (capable of recording neuronal activity over a large area), and, combined with a four-electrode configuration, forms a 64-channel micro-actuable microfilament olfactory bulb cluster array electrode with a three-dimensional spatial arrangement.
[0100] In one embodiment, testing and debugging:
[0101] Appearance quality inspection
[0102] Electrode volume check: Detecting whether the volume of the tested electrode meets the invention objectives.
[0103] See Figure 5 Visually inspect under a microscope whether the number of electrode wires of the 64-conductor electrode is 4×4×4; visually inspect under a microscope whether the physical dimensions of the 64-conductor electrode are 1 mm × 1 mm × 1 mm.
[0104] Spatial array electrode contact arrangement size inspection: Testing the spatial array electrode contact arrangement size
[0105] During inspection, using a calibrated optical microscope (with a large depth of field) with a scale conforming to national standards, the diameter of the electrode bundle is photographed and measured along the electrode axis. After rotating the entire electrode along the axis, the diameters in the length, width, and height directions are recorded. The diameters of the electrode bundle in all three directions are less than 1 mm. In the recorded three directions, the distance between any two contacts along the electrode bundle axis is less than Lx. During testing, the distance between the farthest contact from the end of the electrode bundle and the nearest contact is measured.
[0106] Weight parameter check
[0107] The weight of the tested electrode was checked to ensure it was less than 5g. The electronic balance was first calibrated and zeroed. The weight of the 64-conductor electrode was then measured to check if it met the requirement. Testing showed that the mass of the samples was between 0.9g and 1g, which meets the target requirement.
[0108] Data Acquisition Performance Check
[0109] To determine whether the tested electrode can acquire a field potential.
[0110] Healthy SD rats were selected for electrode implantation surgery. Based on standard rat brain atlases, the implantation area was determined to be 7.28 mm anteriorly and 1.0 mm to the right, with a depth of 2.5-3.5 mm. A 64-lead cluster array electrode was implanted into the right olfactory bulb region of the rats using a stereotactic localization device. The electrodes were fixed to the rat skull with dental cement. After the rats recovered, field potential signals were detected. The rats were anesthetized, and the electrodes were connected to a 32-channel in vivo multichannel neural signal acquisition system (Cerebus) to collect and examine field potential signals.
[0111] After the 64-channel electrodes are implanted into the olfactory bulb, a stable local field potential can be recorded for each channel. See [link to documentation]. Figure 6 .
[0112] Electrical connection test.
[0113] The steps for testing the electrical connection characteristics of the electrodes are as follows:
[0114] Prepare a piece of agar measuring 50mm×50mm×50mm with the same electrical conductivity as the biological tissue.
[0115] Prepare two 10mm×20mm×0.2mm medical-grade 304 stainless steel sheets for later use;
[0116] Two thin metal sheets are inserted into the agar parallel to each other and at the same depth along the length direction, with a spacing of 10 mm between them, and each sheet protruding 10 mm.
[0117] Connect the metal sheets to the positive and negative output terminals of the low-frequency signal generator using alligator clips;
[0118] Set the low-frequency signal generator output to a 1kHz, 100mV sinusoidal voltage signal;
[0119] Gently insert the 64-channel electrode between the two agar metal sheets, at a distance equal to that between the two metal sheets;
[0120] Connect the input terminal of channel 1 of the dual-channel oscilloscope to the output terminal of the low-frequency signal generator, and the input terminal of channel 2 to the 64-channel electrode connection port;
[0121] The analog voltage signal detected in each of the 64 channels was measured from the 64-channel electrode connection port.
[0122] Acceptance criteria: If the waveform displayed on each channel is in phase with the output waveform of the signal generator, and the amplitude is approximately 50mV, with different signal amplitudes across channels and fluctuations between 2.5mV and 10mV, then the electrical connection of that channel is considered acceptable. If there is no signal or the waveforms displayed on adjacent channels have completely identical amplitudes (amplitude difference less than 0.5mV), then the electrical connection of that channel is considered unacceptable. Ensure that all 64 leads are acceptable.
[0123] Although embodiments of the present invention have been described above in conjunction with the accompanying drawings, the present invention is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art can make many other forms based on the guidance of this specification and without departing from the scope of protection of the claims of the present invention, and all of these are within the scope of protection of the present invention.
Claims
1. A method for fabricating a spatial electrode based on a focused ion beam, characterized by, It comprises the following steps: Step 1, the metal wire is drawn into a plurality of electrode wires of a predetermined length and a predetermined diameter, every four electrode wires are aligned and fixed to the electrode wire winding auxiliary equipment by gluing, and then the electrode wire winding auxiliary equipment is rotated counterclockwise for multiple turns and clockwise for multiple turns, and finally the front end is cut off in a flush manner to form a fine wire, wherein every four electrode wires are aligned and fixed to the electrode wire winding auxiliary equipment by gluing, and then the electrode wire winding auxiliary equipment is rotated counterclockwise for 25 turns and clockwise for five turns, and finally the front end is cut off in a flush manner using a tungsten steel; Step 2, a plurality of groups of insulating sleeves are aligned and arranged in a row and fixed to the electrode support, a plurality of groups of fine wires pass through the plurality of groups of insulating sleeves respectively and the front ends are flush, and the ends of the plurality of groups of fine wires are respectively connected to the connector interface and fixed by soldering; Step 3, the fine wire is perforated by using an electrostatic lens to focus an ion beam into a micro-cutting beam, exposing a local cylindrical surface of the electrode wire as a contact point, and the end of the wire is closed using a photosensitive resin; Step 4, the connector interface is fixed to the electrode support, the plurality of groups of fine wires after perforation are respectively inserted into the polyimide tube and the rear end is fixed, the fine wire close to the connector interface is unwound, the insulating sleeve layer is peeled off, one end is inserted through the REF hole of the PCB board and welded, the fine wire is a silver wire, and the excess part is pulled off, the silver wire serves as a reference wire; one end of a silver wire is inserted through the GND via hole of the PCB board and welded, and the excess part is pulled off, the silver wire serves as a ground wire, the fine wire is perforated by the micro-cutting beam to form a square hole of 20*40 microns, the center distance of the square hole is 140 microns and the center is kept in a plane, the insulating sleeve is cut off to expose a local cylindrical surface of the electrode wire as a contact point, and the end of the fine wire is closed using a photosensitive resin to form a cluster electrode in space, each cluster electrode contains 4 titanium wires with a polyimide resin coating and a height difference of 12.5µm.
2. The method of claim 1, wherein, The metal wire includes a tungsten wire or a nichrome wire, and the insulating sleeve is made of polyimide.
3. The method of claim 1, wherein, The metal wire is drawn into a plurality of electrode wires of a diameter of 20 microns and a length of 11 cm by mechanical drawing.
4. The method of claim 1, wherein, The electrode support is formed by 3D printing via PEEK material.
5. The method of claim 1, wherein, The connector interface is an Omnetics interface.
6. A spatial electrode, characterized by The spatial electrode is prepared by the spatial electrode preparation method based on focused ion beam according to any one of claims 1-5.
7. The spatial electrode of claim 6, wherein The spatial electrode includes four electrodes, and the four electrodes constitute a micro-driven micro-wire olfactory bulb cluster array electrode with a three-dimensional spatial arrangement.
Citation Information
Patent Citations
Minimally invasive splaying microfiber electrode array and methods of fabricating and implanting the same
US20170007824A1