CN117426775A - Cell resolution tungsten-based microelectrode array for deep human brain and manufacturing method - Google Patents

Cell resolution tungsten-based microelectrode array for deep human brain and manufacturing method Download PDF

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CN117426775A
CN117426775A CN202311476173.6A CN202311476173A CN117426775A CN 117426775 A CN117426775 A CN 117426775A CN 202311476173 A CN202311476173 A CN 202311476173A CN 117426775 A CN117426775 A CN 117426775A
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tungsten
microelectrode array
sites
based microelectrode
site
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莫凡
蔡新霞
王蜜霞
宋轶琳
刘军涛
罗金平
景露易
刘瑶瑶
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Aerospace Information Research Institute of CAS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25Bioelectric electrodes therefor
    • A61B5/263Bioelectric electrodes therefor characterised by the electrode materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/242Detecting biomagnetic fields, e.g. magnetic fields produced by bioelectric currents
    • A61B5/245Detecting biomagnetic fields, e.g. magnetic fields produced by bioelectric currents specially adapted for magnetoencephalographic [MEG] signals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25Bioelectric electrodes therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25Bioelectric electrodes therefor
    • A61B5/279Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A61B5/293Invasive

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Abstract

The invention discloses a cell resolution tungsten-based microelectrode array for deep brain and a manufacturing method thereof, which relate to the field of clinical nerve electrodes and are used for detecting and recording electrophysiological signals of neurons in deep brain regions of the human brain, and comprise the following steps: the electrode comprises a tungsten-based microelectrode array tip, a grounding site, an electrophysiological signal detection site, a lead wire, a bonding pad site and a tungsten-based microelectrode array substrate. In the manufacturing process, a strip-shaped tungsten rod with high biocompatibility and excellent hardness is used as a base material, and grounding sites, electrophysiological signal detection sites, leads and bonding pad sites are processed on four sides of the tungsten rod through an MEMS (micro electro mechanical System) process. Because of the extremely high resolution of electrophysiological sites in the array, the firing activity of individual neurons can be captured. In the signal detection process, the invention can determine the specific direction of the signal source relative to the tungsten rod electrode, thereby realizing large-scale and multidirectional signal recording in the deep part of the human brain and accurate brain region positioning.

Description

Cell resolution tungsten-based microelectrode array for deep human brain and manufacturing method
Technical Field
The invention relates to the field of clinical nerve electrodes, in particular to a cell resolution tungsten-based microelectrode array for deep human brain and a manufacturing method thereof.
Background
Advances in neuroscience research, particularly understanding of human brain function and disease mechanisms, provide a powerful support for improving clinical diagnosis and treatment. In this regard, electrophysiological signal detection and recording techniques play a key role in understanding neuronal activity, neural circuit function, and abnormalities associated with brain function. However, due to the complex and difficult detection of human brain deep structures, existing electrophysiological recording techniques are challenging in achieving high resolution, multidirectional brain region localization, and signal recording at the single neuron level.
Currently, electrophysiological recording techniques widely used in clinic mainly include electroencephalography (EEG) and Magnetoencephalography (MEG). However, high resolution recordings for deep brain regions are very limited, as they can only record brain surface activity. On the other hand, silicon-based microelectrodes are used as a common electrophysiological recording tool, and have been remarkably successful in small animal models due to the characteristics of high channel density and small size. However, applying these techniques to deep human brain, there are still a number of challenges due to the specific nature of neural tissue, the need for cell resolution, and electrode stability. SEEG electrodes (Stereo Electroencephalography, SEEG for short) are a minimally invasive technique aimed at implanting electrodes deep into the human brain during neurosurgery to record and monitor electrical activity in a specific brain region in real time. These electrodes can provide the clinician with valuable information about seizure origin areas, functional areas around brain tumors, and other neurological disorders.
In a conventional SEEG procedure, the physician may make a series of small incisions in the scalp and then implant the electrodes individually into the intended brain region. The specific location of the electrodes is planned based on the patient's brain scan image and clinical requirements. Typically, multiple electrode channels are provided on each electrode to simultaneously record electrical activity of multiple brain tissues at different depths. The channels can collect electrical signals of brain regions in real time and help doctors locate abnormal electrical activities such as the origin of epileptic seizures.
The SEEG electrodes are typically relatively large for recording the overall electrical activity of the brain region. However, brain function and cognitive processes often involve the activity of individual neurons or groups of neurons. Because of the large size of the segg electrodes, it is difficult to accurately capture electrophysiological signals at the individual neuron level. Such signals are important for understanding the microscopic circuitry, information transfer, and neural encoding of the brain, but seg does not provide sufficient spatial resolution to capture these subtle activities. Second, due to the structural complexity of the brain interior, multiple electrodes need to be placed in different brain regions to obtain comprehensive electrophysiological information. However, the placement of the see electrode is constrained by anatomical limitations and surgical risks, and thus the number of channels available in a single implantation is limited.
Meanwhile, the traditional microelectrode manufacturing method cannot meet the requirement of performing high-channel electrophysiological recording with high cell resolution in the deep part of the human brain. Accordingly, there is a need for a carefully designed and optimized fabrication method to ensure that tungsten-based microelectrode arrays exhibit excellent stability, biocompatibility and high resolution characteristics during use.
Disclosure of Invention
Aiming at the technical problems, the invention provides a cell resolution tungsten-based microelectrode array for deep human brain and a manufacturing method thereof, wherein the tungsten-based microelectrode array is used for realizing detection and recording of cell resolution deep human brain electrophysiological signals. Tungsten has excellent mechanical strength and electrical conductivity as an electrode material, and is expected to exhibit stability in long-term recording. By optimizing the manufacturing method, the tungsten-based microelectrode array can realize high channel density and micro size, so that high-resolution recording of deep micro neurons of the human brain is realized while the stability of the electrode is maintained.
The invention comprises a tungsten-based microelectrode array tip, a grounding site, an electrophysiological signal detection site, a lead wire, a bonding pad site and a tungsten-based microelectrode array substrate. In the manufacturing process, a strip-shaped tungsten rod with high biocompatibility and excellent hardness is used as a base material, and grounding sites, electrophysiological signal detection sites, leads and bonding pad sites are processed on four sides of the tungsten rod through an MEMS (micro electro mechanical System) process. Because of the extremely high resolution of electrophysiological sites in the array, the firing activity of individual neurons can be captured. In the signal detection process, the invention can determine the specific direction of the signal source relative to the tungsten rod electrode, thereby realizing large-scale and multidirectional signal recording in the deep part of the human brain and accurate brain region positioning.
The manufacturing method of the present invention relates to new materials (tungsten) in the field of micromachining and improvements in high channel clinical microelectrode arrays. In particular, the manufacturing and handling process of tungsten electrodes requires consideration of how to achieve good coupling with neural tissue to obtain accurate and stable electrophysiological signal recordings. In addition, advanced technologies in interdisciplinary fields such as micro-nano processing technology, material science and bioengineering are also involved in the manufacturing process to ensure the performance and reliability of the final product.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a cell resolution tungsten-based microelectrode array for use in the deep human brain, comprising: the electrode comprises a tungsten-based microelectrode array tip, a grounding site, an electrophysiological signal detection site, a lead wire, a bonding pad site and a tungsten-based microelectrode array substrate; the tip of the tungsten-based microelectrode array, the grounding site, the electrophysiological signal detection site, the lead wire, the bonding pad site and the tungsten-based microelectrode array substrate form a whole, the tip of the tungsten-based microelectrode array is positioned at the bottommost part of the cell resolution tungsten-based microelectrode array, and the grounding site, the electrophysiological signal detection site, the lead wire and the bonding pad site are arranged on the surface of the tungsten-based microelectrode array substrate and are connected with the bonding pad site through the lead wire.
Further, the cell resolution tungsten-based microelectrode array for the deep part of the human brain is formed by a tungsten rod, the cross section of which is square with a side length of 1mm and the length of which is 5 cm-10 cm.
Further, the distribution of the electrophysiological detection points is adjusted according to the detection brain region to match the shape of the detection brain region.
Further, the area of the grounding locus is more than 10 times that of the electrophysiological signal detection locus, and a more stable potential can be provided in electrophysiological signal recording.
Further, the electrophysiological signal detection sites are round with the diameter of 2-30 microns, and the number of the electrophysiological signal detection sites on each surface of the tungsten rod is 8-128.
Further, the line width of the leads is 10-20 μm, and the line spacing is 2-20 μm or more.
Further, the pad sites are square with a side length of 100-500 μm, and the spacing between adjacent pad sites is 10-50 μm.
The invention also discloses a manufacturing method of the cell resolution tungsten-based microelectrode array for the deep part of the human brain, which comprises the following steps:
s1: cutting a tungsten plate: performing linear cutting on the tungsten plate by using a numerical control machine tool to obtain a tungsten rod with a required length;
s2: cleaning a tungsten rod: cleaning the cut tungsten rod to expose the clean tungsten surface;
s3: tungsten rod groove spin coating: spin coating photoresist on the electrode grooves of the tungsten rod;
s4: splicing tungsten bars: putting the tungsten rod into a tungsten rod electrode groove to realize splicing;
s5: depositing a base insulating layer: depositing a first layer of SiO on the surface of the spliced tungsten rod 2 The insulating layer is used as a base insulating layer, and the thickness is 800 nm-2 mu m;
s6: sputtering a metal layer: in SiO 2 Surface spin of insulating layerCoating photoresist, photoetching, sputtering metal, and then stripping redundant metal to leave the positions of electrophysiology signal detection sites, leads and bonding pad sites;
s7: depositing a surface insulating layer: depositing a second layer of SiO over the electrophysiological signal detection sites, leads, pad sites 2 The insulating layer is used as a surface insulating layer, and the thickness is 800 nm-2 mu m;
s8: etching sites: spin coating photoresist, photoetching and etching on the surface insulating layer until electrophysiological signal detection sites and bonding pad sites are exposed;
repeating the steps S4 to S8 until all 4 surfaces of the tungsten rod are processed;
s9: and (5) packaging and testing.
Further, the step S2 includes: etching the tips of the tungsten-based microelectrode arrays by electrochemical means, i.e. immersing the portions of the tungsten rods forming the tips of the tungsten-based microelectrode arrays in a sodium hydroxide solution, and gradually etching them into a sharp shape by applying a voltage to the surface of the tungsten rods.
Further, in the step S3, the tungsten rod groove comprises a groove bottom and side walls and is used for accommodating the tungsten rod with the length of 1 cm-10 cm.
The beneficial effects are that:
(1) The invention adopts a tungsten substrate with hardness and good biocompatibility, and can be used for deep brain of people;
(2) The invention realizes multichannel electrophysiological signal recording;
(3) The invention enables the recording of single cell level neuronal signals for the human brain;
(4) The invention can distinguish neuron signals in different directions.
The tungsten-based microelectrode array and the manufacturing method thereof have the capability of detecting and recording high-resolution multidirectional electrophysiological signals in the deep part of the human brain. By combining the practical requirements of clinical electrodes and the technical advantages of silicon-based microelectrodes, the invention is expected to bring important breakthrough to neuroscience research and clinical application, thereby further exploring the mysterious of human brain and promoting the understanding and treatment of related diseases of the nervous system.
Drawings
FIG. 1 is a schematic diagram of a cell resolution tungsten-based microelectrode array of the present invention for use in the deep human brain;
FIG. 2 is a schematic view of a tungsten-based microelectrode array tip;
FIG. 3 is a schematic view of a tungsten rod electrode cell;
FIG. 4 is a flow chart of a method of manufacturing a cell resolution tungsten-based microelectrode array for use in the deep brain of a person of the present invention.
Detailed Description
Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. It should be understood that the description is only illustrative and is not intended to limit the scope of the invention. In the following detailed description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the invention. It may be evident, however, that one or more embodiments may be practiced without these specific details. In addition, in the following description, descriptions of well-known structures and techniques are omitted so as not to unnecessarily obscure the present invention.
The invention provides a cell resolution tungsten-based microelectrode array for deep human brain, which is a high-channel density tungsten-based microelectrode array and can realize cell resolution electrophysiological signal detection in deep brain areas, such as amygdala.
As shown in fig. 1 and 2, the cell resolution tungsten-based microelectrode array for deep brain of human of the present invention includes a tungsten-based microelectrode array tip 1, a grounding site 2, an electrophysiological signal detection site 3, a lead 4, a pad site 5, and a tungsten-based microelectrode array substrate 6.
The tungsten-based microelectrode array tip 1, the grounding site 2, the electrophysiological signal detection site 3, the lead 4, the bonding pad site 5 and the tungsten-based microelectrode array substrate 6 are integrated, the tungsten-based microelectrode array tip 1 is positioned at the bottommost part of the cell resolution tungsten-based microelectrode array, the grounding site 2, the electrophysiological signal detection site 3, the lead 4 and the bonding pad site 5 are arranged on the surface of the tungsten-based microelectrode array substrate 6, and the grounding site 2 and the electrophysiological signal detection site 3 are connected with the bonding pad site 5 through the lead 4.
Preferably, the tungsten-based microelectrode array contains 128 channels on each face, providing a high channel density. The electrophysiological signal detection site 3 is designed at the tip 1 of the tungsten-based microelectrode array, which can realize efficient detection of cell activity in the target area. The layout of the electrophysiological signal detection sites 3 of the tungsten-based microelectrode array is tailored to the shape and configuration of the amygdala for specific research objectives, such as electrophysiological activity of the amygdala.
As shown in fig. 4, the method for manufacturing the cell resolution tungsten-based microelectrode array for deep human brain of the present invention includes the steps of:
s1: cutting a tungsten plate: performing linear cutting on the tungsten plate by using a numerical control machine tool to obtain a tungsten rod with a required length;
s2: cleaning a tungsten rod: cleaning the cut tungsten rod to expose the clean tungsten surface;
s3: tungsten rod groove spin coating: spin coating photoresist on the electrode grooves of the tungsten rod;
s4: splicing tungsten bars: putting the tungsten rod into a tungsten rod electrode groove to realize splicing;
s5: depositing a base insulating layer: depositing a first layer of SiO on the surface of the spliced tungsten rod 2 The insulating layer is used as a base insulating layer, and the thickness is 800 nm-2 mu m;
s6: sputtering a metal layer: in the first layer SiO 2 Spin coating photoresist, photoetching and sputtering metal on the surface of the insulating layer, and then stripping off redundant metal to leave the positions of the electrophysiology signal detection site 3, the lead 4 and the bonding pad site 5;
s7: depositing a surface insulating layer: depositing a second layer of SiO over the electrophysiological signal detection sites 3, the leads 4, and the pad sites 5 2 The insulating layer is used as a surface insulating layer, and the thickness is 800 nm-2 mu m;
s8: etching sites: spin coating photoresist on the surface insulating layer, photoetching and etching until all sites are exposed;
steps S4 to S8 are repeated until the number of electrophysiological signal detection sites 3 on each face of the tungsten rod reaches 128.
And S9, packaging and testing are carried out, so that the performance and stability of the tungsten-based microelectrode array are ensured.
As shown in fig. 3, the tungsten rod groove comprises a groove bottom 7 and side walls 8, and can accommodate tungsten rods with the length of 1 cm-10 cm.
In this way, the present invention provides a tungsten-based microelectrode array with high channel density and positioning for specific brain regions making it an ideal tool for cell resolution electrophysiological signal detection in deep brain regions. In particular, for the study of target areas such as amygdala, the tungsten-based microelectrode array is capable of providing high quality electrophysiological data, helping to gain insight into neuronal activity and brain circuit function.
It is noted that the innovations of the present invention are not limited to hardware aspects alone. The signal acquisition, data processing and analysis algorithms matched with the electrode array are also key points for realizing efficient and accurate recording and interpretation of electrophysiological signals. By combining advanced signal processing techniques with tungsten-based microelectrode arrays, researchers can achieve deeper neural activity interpretation, thereby providing more accurate tools and methods for neuroscience research.
It will be understood by those skilled in the art that while the present invention has been shown and described with reference to particular exemplary embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims and their equivalents. The scope of the disclosure should, therefore, not be limited to the above-described embodiments, but should be determined not only by the following claims, but also by the equivalents of the following claims.

Claims (10)

1. A cell resolution tungsten-based microelectrode array for use in the deep brain of a human, comprising: a tungsten-based microelectrode array tip (1), a grounding site (2), an electrophysiological signal detection site (3), a lead (4), a bonding pad site (5) and a tungsten-based microelectrode array substrate (6); the tungsten-based microelectrode array tip (1), the grounding site (2), the electrophysiological signal detection site (3), the lead (4), the bonding pad site (5) and the tungsten-based microelectrode array substrate (6) form a whole, the tungsten-based microelectrode array tip (1) is positioned at the bottommost part of the cell resolution tungsten-based microelectrode array, the grounding site (2), the electrophysiological signal detection site (3), the lead (4) and the bonding pad site (5) are arranged on the surface of the tungsten-based microelectrode array substrate (6), and the grounding site (2) and the electrophysiological signal detection site (3) are connected with the bonding pad site (5) through the lead (4).
2. The cell resolution tungsten based microelectrode array for deep human brain according to claim 1, wherein the material of the cell resolution tungsten based microelectrode array for deep human brain is a tungsten rod with a cross section of square with a side length of 1mm and a length of 5cm to 10cm.
3. The cell resolution tungsten based microelectrode array for deep human brain according to claim 1, characterized in that the distribution of electrophysiological detection sites (3) is adjusted to match the shape of the detection brain region according to the detection brain region.
4. The cell-resolution tungsten-based microelectrode array for deep human brain according to claim 1, being characterized in that the area of the grounding sites (2) is more than 10 times larger than the electrophysiological signal detection sites (3), providing a more stable potential at the time of electrophysiological signal recording.
5. The cell resolution tungsten-based microelectrode array for deep human brain according to claim 2, wherein the electrophysiological signal detection sites (3) are circular with a diameter of 2-30 micrometers, and the number of electrophysiological signal detection sites (3) on each side of the tungsten rod is 8-128.
6. The cell resolution tungsten based microelectrode array for deep human brain according to claim 1, wherein the line width of the lead (4) is 10 to 20 μm and the line spacing is 2 to 20 μm.
7. The cell resolution tungsten based microelectrode array for deep human brain according to claim 1, wherein the pad sites (5) are squares with a side length of 100 to 500 μm and the pitch of adjacent pad sites (5) is 10 to 50 μm.
8. Method for manufacturing a cell-resolved tungsten-based microelectrode array for deep human brain according to one of the claims 1 to 7, characterised in that it comprises the following steps:
s1: cutting a tungsten plate: performing linear cutting on the tungsten plate by using a numerical control machine tool to obtain a tungsten rod with a required length;
s2: cleaning a tungsten rod: cleaning the cut tungsten rod to expose the clean tungsten surface;
s3: tungsten rod groove spin coating: spin coating photoresist on the electrode grooves of the tungsten rod;
s4: splicing tungsten bars: putting the tungsten rod into a tungsten rod electrode groove to realize splicing;
s5: depositing a base insulating layer: depositing a first layer of SiO on the surface of the spliced tungsten rod 2 The insulating layer is used as a base insulating layer, and the thickness is 800 nm-2 mu m;
s6: sputtering a metal layer: in the first layer SiO 2 Spin coating photoresist, photoetching and sputtering metal on the surface of the insulating layer, and then stripping off redundant metal to leave the positions of electrophysiology signal detection sites (3), leads (4) and bonding pad sites (5);
s7: depositing a surface insulating layer: depositing a second layer of SiO over the electrophysiological signal detection sites (3), the leads (4), and the pad sites (5) 2 The insulating layer is used as a surface insulating layer, and the thickness is 800 nm-2 mu m;
s8: etching sites: spin coating photoresist, photoetching and etching on the surface insulating layer until electrophysiological signal detection sites (3) and bonding pad sites (5) are exposed;
repeating the steps S4 to S8 until all 4 surfaces of the tungsten rod are processed;
s9: and (5) packaging and testing.
9. The manufacturing method according to claim 8, wherein the S2 includes: the tungsten-based microelectrode array tip (1) is etched by an electrochemical method, namely, a tungsten rod forming the tungsten-based microelectrode array tip (1) is soaked in sodium hydroxide solution, and then the tungsten rod is gradually etched into a sharp shape by applying voltage on the surface of the tungsten rod.
10. The manufacturing method according to claim 8, wherein in S3, the tungsten rod groove comprises a groove bottom (7) and side walls (8) for accommodating a tungsten rod having a length of 1cm to 10cm.
CN202311476173.6A 2023-11-08 2023-11-08 Cell resolution tungsten-based microelectrode array for deep human brain and manufacturing method Pending CN117426775A (en)

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CN117426775A true CN117426775A (en) 2024-01-23

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