CN115381458A - Brain electrode device, preparation method thereof, electrode device and electronic equipment - Google Patents
Brain electrode device, preparation method thereof, electrode device and electronic equipment Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/25—Bioelectric electrodes therefor
- A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
- A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
- A61B5/293—Invasive
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
- A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/16—Details of sensor housings or probes; Details of structural supports for sensors
Abstract
Provided are a brain electrode device, a preparation method thereof, an electrode device and electronic equipment. The brain electrode device comprises: a flexible substrate including a first portion and a plurality of second portions separated from each other; a probe pad array including a plurality of contact pads formed in the first portion; a plurality of deep electrodes and a plurality of cortical electrodes formed in respective end sections of the plurality of second portions distal from the first portion; a plurality of leads formed in the plurality of second portions to electrically connect the plurality of deep electrodes and the plurality of skin electrodes to the corresponding contact pads, respectively; each end section of the second plurality of portions includes a first type of end section in which the plurality of deep electrodes are formed and a second type of end section in which the plurality of skin electrodes are formed, the second type of end section being provided with a plurality of through holes through the flexible substrate, each through hole being sized to allow one or more corresponding first type of end sections to pass through.
Description
Technical Field
The application relates to the technical field of microelectronic packaging interconnection, in particular to a brain electrode device, a preparation method of the brain electrode device, an electrode device and electronic equipment.
Background
A brain-machine interface, sometimes also referred to as a "brain port" or "brain-machine fusion sense", is a direct connection path established between a human or animal brain (or a culture of brain cells) and an external device. The brain-computer interface has received wide attention from the scientific research and industrial fields all over the world as a multidisciplinary cross technology. The flexible brain-computer interface is used as a branch of the brain-computer interface, and is considered as the final form of the brain-computer interface due to the superior biocompatibility.
The existing flexible brain electrode device comprises a bonding pad and a plurality of flexible electrodes connected with the bonding pad, wherein the tail end of each flexible electrode is provided with a recording site, and the tail ends of the flexible electrodes are implanted into the brain of an organism to detect electroencephalogram signals. In the related art, flexible brain electrode devices are classified into flexible deep electrode devices and flexible cortical electrode devices. The flexible deep electrode device is characterized in that the electrodes arranged at the tail end of each flexible electrode are deep electrodes, and the deep electrodes can collect brain signals of different depths in brain tissues. The flexible cortical electrode device is a cortical electrode which is an electrode arranged at the tail end of the flexible electrode, and the cortical electrode can collect brain signals in a specific area on the surface of brain tissues.
Disclosure of Invention
An object of this application is to provide a brain electrode assembly that can gather regional cortical signals while gathering the regional brain signal of the different degree of depth in this region.
Embodiments of the first aspect of the present application provide a brain electrode apparatus comprising: a flexible substrate comprising a first portion at a first end of the brain electrode apparatus and a plurality of second portions extending from the first portion to a second end of the brain electrode apparatus, the second end being opposite the first end; a probe pad array including a plurality of contact pads formed in the first portion; a plurality of deep electrodes and a plurality of cortical electrodes formed in respective end segments of the plurality of second portions distal to the first portion, the end segments acting as probes for implantation into the brain of an organism; and a plurality of leads formed in the plurality of second portions to electrically connect respective ones of the plurality of deep electrodes and the plurality of cortical electrodes to respective ones of the plurality of contact pads, respectively, wherein each end section of the plurality of second portions includes a first type end section that acts as a deep probe for implantation into a deep brain region of a living being, the plurality of deep electrodes being formed in the first type end section, wherein each end section of the plurality of second portions further includes a second type end section that acts as a cortical flexible membrane for placement on a cortical surface of the living being, the plurality of cortical electrodes being formed in the second type end section, and wherein the second type end section is provided with a plurality of through holes through the flexible substrate, each through hole being sized to allow passage therethrough of one or more corresponding first type end sections.
Embodiments of a second aspect of the present application provide an electrode device comprising a brain electrode device according to any one of the above; and a data adaptor electrically connected to the plurality of contact pads in the probe pad array, configured to transmit or receive signals to or from the plurality of contact pads.
Embodiments of a third aspect of the present application provide an electronic device comprising an electrode arrangement as described above.
Embodiments of a fourth aspect of the present application provide a method of making a brain electrode device, the method comprising: forming a first flexible base layer on a support substrate, the first flexible base layer comprising a first region at a first end of the brain electrode apparatus and a plurality of second regions extending from the first region to a second end of the brain electrode apparatus, the second end being opposite the first end; forming a metal pattern layer on the first flexible base layer, the metal pattern layer including a probe pad array including a plurality of contact pads formed on a first region, a plurality of deep electrodes and a plurality of skin electrodes formed in respective end sections of a plurality of second regions remote from the first region, and wherein the respective end sections of the plurality of second regions include a first type end section in which the plurality of deep electrodes are formed and a second type end section in which the plurality of skin electrodes are formed, and a plurality of leads formed on the plurality of second regions to electrically connect respective ones of the plurality of deep electrodes and the plurality of skin electrodes to respective ones of the plurality of contact pads, respectively; covering a second flexible substrate layer on the first flexible substrate layer on which the metal pattern layer is formed; etching the second flexible base layer and the first flexible base layer to expose the plurality of contact pads, the plurality of deep electrodes and the plurality of skin electrodes, forming a first portion of the pattern corresponding to the first area and a plurality of second portions of the pattern corresponding to the plurality of second areas, and etching a plurality of through holes through the second flexible base layer and the first flexible base layer in second-type end sections of the plurality of second portions, wherein each through hole has a size that allows one or more first-type end sections of the plurality of second portions to pass through; and removing a portion of the support substrate other than the first support substrate portion, the first support substrate portion corresponding to the first portion.
According to the brain electrode device of the embodiment of the present application, the plurality of second portions include both the first type end segment serving as a deep probe and the second type end segment serving as a cortical flexible membrane, and thus the brain electrode device can detect brain signals at different depths in the brain tissue as well as brain signals of specific regions on the surface of the brain tissue. Also, a through hole is provided in the second type of end section acting as a cortical flexible membrane through which the first type of end section acting as a deep probe can be passed for implantation in the deep brain region. Therefore, the cortical electroencephalogram signal and the deep electroencephalogram signal can be acquired simultaneously in the same brain area, namely, the deep brain signal and the cortical area brain signal in the same brain area can be acquired simultaneously, and the brain signal can be analyzed and detected conveniently. In addition, the through holes arranged on the second type end sections can also improve the stress of the second type end sections, improve the flexibility of the second type end sections and further be beneficial to improving the fitting property of the second type end sections and the surface of brain tissue.
The foregoing description is only an overview of the technical solutions of the present application, and the present application can be implemented according to the content of the description in order to make the technical means of the present application more clearly understood, and the following detailed description of the present application is given in order to make the above and other objects, features, and advantages of the present application more clearly understandable.
Drawings
In the drawings, like reference numerals refer to the same or similar parts or elements throughout the several views unless otherwise specified. The figures are not necessarily to scale. It is appreciated that these drawings depict only some embodiments in accordance with the disclosure and are therefore not to be considered limiting of its scope.
Fig. 1 is a schematic structural diagram of a brain electrode apparatus provided in some embodiments of the present application;
fig. 2 is a schematic structural view of a first type of end segment of a second part of a brain electrode apparatus according to some embodiments of the present application;
fig. 3 is a schematic diagram of a second type of end segment of a second portion of a brain electrode assembly according to some embodiments of the present application;
fig. 4 is a schematic cross-sectional view of a first type of end segment through a through-hole in a second type of end segment in a brain electrode device according to some embodiments of the present application;
FIG. 5 is a schematic illustration of an exploded view of an electrode assembly according to some embodiments of the present disclosure;
fig. 6 is a flow chart of a method of preparing a brain electrode assembly according to some embodiments of the present application;
fig. 7 is a schematic diagram of a process for preparing a brain electrode device according to some embodiments of the present application.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to the accompanying drawings. The following examples are merely used to more clearly illustrate the technical solutions of the present application, and therefore are only examples, and the protection scope of the present application is not limited thereby.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs; the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application; the terms "including" and "having," and any variations thereof, in the description and claims of this application and the description of the above figures are intended to cover non-exclusive inclusions.
In the description of the embodiments of the present application, the technical terms "first", "second", and the like are used only for distinguishing different objects, and are not to be construed as indicating or implying relative importance or implicitly indicating the number, specific order, or primary-secondary relationship of the technical features indicated. In the description of the embodiments of the present application, "a plurality" means two or more unless specifically defined otherwise.
Reference herein to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the application. The appearances of the phrase in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. It is explicitly and implicitly understood by one skilled in the art that the embodiments described herein can be combined with other embodiments.
In the description of the embodiments of the present application, the term "and/or" is only one kind of association relationship describing an associated object, and means that three relationships may exist, for example, a and/or B, and may mean: a exists alone, A and B exist simultaneously, and B exists alone. In addition, the character "/" herein generally indicates that the former and latter related objects are in an "or" relationship.
In the description of the embodiments of the present application, the term "plurality" refers to two or more (including two), and similarly, "plural sets" refers to two or more (including two sets), "plural pieces" refers to two or more (including two pieces).
In the description of the embodiments of the present application, the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", and the like, indicate the directions or positional relationships indicated in the drawings, and are only for convenience of description of the embodiments of the present application and for simplicity of description, but do not indicate or imply that the referred device or element must have a specific direction, be constructed and operated in a specific direction, and thus, should not be construed as limiting the embodiments of the present application.
In the description of the embodiments of the present application, unless otherwise explicitly stated or limited, the terms "mounted," "connected," "fixed," and the like are used in a broad sense, and for example, may be fixedly connected, detachably connected, or integrated; mechanical connection or electrical connection is also possible; either directly or indirectly through intervening media, either internally or in any other relationship. Specific meanings of the above terms in the embodiments of the present application can be understood by those of ordinary skill in the art according to specific situations.
Please refer to fig. 1, fig. 2, fig. 3 and fig. 4. Fig. 1 is a schematic structural diagram of a brain electrode device 100 according to some embodiments of the present disclosure. Fig. 2 is a schematic diagram illustrating a first type end section 1021 of a second portion of a brain electrode device according to some embodiments of the present application. Fig. 3 is a schematic diagram of a second type of end segment 1022 of a second portion of a brain electrode assembly according to some embodiments of the present application. Fig. 4 is a schematic cross-sectional view of a first type of end segment through a through-hole in a second type of end segment in a brain electrode device according to some embodiments of the present application.
It should be noted that fig. 1, 2, 3 and 4 are only used for schematically showing some features of the structures, and do not limit the actual number and size of the structures. For example, fig. 1 only schematically shows two second portions, one of which has two-stage segments, and leads in each second portion, and the like, wherein the number of second portions, the number of stages of segments of the second portions, and the number of leads, and the like, do not represent the number of these structures in an actual product. Similarly, the number of electrodes and leads in fig. 2 and 3 is not intended to represent the number of these structures in an actual product, and is not intended to limit the present application. In fig. 4, a partial cross section of a second type of tip segment of the brain electrode device and a first type of tip segment of a through hole passing through the second type of tip segment are taken, it being understood that structures such as a through hole, a skin layer electrode, and a contact pad of the brain electrode device are only schematically illustrated, and the number and size of the structures are not representative of the number and size of the structures in an actual product.
A first aspect of the present disclosure provides a brain electrode apparatus 100. As shown in fig. 1, 2 and 3, the brain electrode device 100 includes a flexible substrate 10, and a probe pad array, a plurality of deep electrodes 13, a plurality of cortical electrodes 14 and a plurality of leads 12 in the flexible substrate 10.
The flexible substrate 10 comprises a first part 101 and a plurality of second parts 102, the first part 101 being located at a first end of the brain electrode apparatus and the plurality of second parts 102 extending from the first part 101 to a second end of the brain electrode apparatus, the second end being opposite the first end.
It will be appreciated that the flexible substrate 10 serves to carry and protect the probe pad array, the plurality of deep electrodes 13, the plurality of cortical electrodes 14 and the plurality of leads 12. In some embodiments, as shown in fig. 4, the flexible substrate 10 may include a first flexible substrate layer 1001 and a second flexible substrate layer 1002 disposed in a stack, with the probe pad array, the plurality of deep electrodes 13, the plurality of cortical electrodes 14, and the plurality of leads 12 being located between the first flexible substrate layer 1001 and the second flexible substrate layer 1002. In one example, the materials of the first flexible substrate layer 1001 and the second flexible substrate layer 1002 may be the same or different, and specifically, a Polyimide (PI) material may be used.
The probe pad array includes a plurality of contact pads (contact pads) 11, and the plurality of contact pads 11 are formed in the first portion 101 of the flexible substrate 10 for electrical connection with an external circuit. In the example of fig. 4, the second flexible base layer 1002 is provided with contact holes (contact holes) 10a for exposing the plurality of contact pads 11 so that the contact pads 11 can be electrically connected to an external circuit.
A plurality of deep electrodes 13 and a plurality of cortical electrodes 14 are formed in respective end segments of the plurality of second portions 102 distal to the first portion 101, the end segments acting as probes for implantation into the brain of an organism. The plurality of deep electrodes 13 and the plurality of cortical electrodes 14 are used to acquire brain signals or output stimulation signals to brain tissue. The deep electrode 13 is used for collecting brain signals at different depths in the brain tissue or outputting stimulation signals to different depths of the brain tissue. The cortical electrodes 14 are used to collect brain signals from or output stimulation signals to specific areas of the brain tissue surface. The second flexible substrate layer 1002 is provided with connection holes for exposing the plurality of deep electrodes 13 and the plurality of cortical electrodes 14, so that the plurality of deep electrodes 13 and the plurality of cortical electrodes 14 can contact with brain tissue to realize brain signal acquisition or stimulation signal output to the brain tissue. The connection hole 10b exposing the skin layer electrode 14 is provided in the cross section illustrated in fig. 4.
A plurality of leads 12 are formed in the plurality of second portions 102 to electrically connect respective ones of the plurality of deep electrodes 13 and the plurality of cortical electrodes 14 to respective ones of the plurality of contact pads 11, respectively.
It is understood that the plurality of leads 12 include a plurality of leads 12 in one-to-one correspondence with the plurality of deep electrodes 13, and each deep electrode 13 is connected to one contact pad 11 by one lead 12 corresponding thereto, and further connected to an external circuit. The plurality of leads 12 further include a plurality of leads 12 corresponding to the plurality of skin electrodes 14 one to one, and each skin electrode 14 is connected to one contact pad 11 through one lead 12 corresponding thereto, and further connected to an external circuit. In one example, the plurality of contact pads 11 are connected to the chip through a data adapter, thereby electrically connecting the plurality of deep electrodes 13 and the plurality of cortical electrodes 14 with the circuitry of the chip.
According to some embodiments, each end section of the plurality of second portions 102 comprises a first type end section 1021, as shown in fig. 2, the first type end section 1021 acting as a deep probe for implantation into a deep brain region of a living being, the plurality of deep electrodes 13 being formed in the first type end section 1021. In one example, the first type end section 1021 is in the shape of an elongated needle for implantation inside brain tissue such that the deep electrode 13 therein can be in contact with the deep brain tissue to enable acquisition of brain signals at different depths within the brain tissue or output of stimulation signals to different depths of the brain tissue.
Further, each end section of the plurality of second portions 102 further comprises a second-type end section 1022, as shown in fig. 3, the second-type end section 1022 acting as a cortical flexible membrane for placement on a cortical surface of the organism, the plurality of cortical electrodes 14 being formed in the second-type end section 1022. In one example, the second type end section 1022 is planar so as to be attached to the surface of the cerebral cortex, such that the cortical electrodes 14 therein can contact the surface of the cerebral tissue, thereby achieving the collection of brain signals in a specific region of the surface of the cerebral tissue or the output of stimulation signals to a specific region of the surface of the cerebral tissue.
In one example, the second type end section 1022 is provided with a plurality of through holes 10c extending through the flexible substrate 10, each through hole 10c being sized to allow one or more corresponding first type end sections 1021 to pass through.
In the example of fig. 4, the flexible substrate 10 includes a first flexible substrate layer 1001 and a second flexible substrate layer 1002 disposed in a stack. The through-holes 10c avoid the plurality of skin electrodes 14 between the first and second flexible substrate layers 1001 and 1002 and penetrate the first and second flexible substrate layers 1001 and 1002.
In the example of fig. 4, the through hole 10c allows one first type end section 1021 to pass through. In practical applications, it is also possible that the through hole 10c allows two or more end sections 1021 of the first type to pass through.
In the brain electrode device 100 according to the embodiment of the present application, the plurality of second portions 102 includes both the first type end section 1021 serving as a deep probe and the second type end section 1022 serving as a cortical flexible membrane, and thus, the brain electrode device 100 can detect brain signals at different depths within the brain tissue as well as brain signals at specific regions of the surface of the brain tissue. Also, a through hole 10c is provided in the second type end section 1022 acting as a cortical flexible membrane, through which through hole 10c the first type end section 1021 acting as a deep probe can be passed for implantation in the deep brain region. Therefore, the cortical electroencephalogram signal and the deep electroencephalogram signal can be acquired simultaneously in the same brain area, namely, the deep brain signal and the cortical area brain signal in the same brain area can be acquired simultaneously, and the brain signal can be analyzed and detected conveniently.
In addition, the through holes 10c formed in the second type end sections 1022 can also improve the stress of the second type end sections 1022, increase the flexibility of the second type end sections 1022, and further facilitate improving the conformability of the second type end sections 1022 and the brain tissue surface.
According to some embodiments, at least one second portion 102 of the plurality of second portions 102 comprises N stages of segmentation, the N stages of segmentation being arranged sequentially along a direction from the first end to the second end, and the nth stage of segmentation of the second portion 102 comprises each end section of the second portion 102, wherein N is an integer greater than or equal to 2. In other words, the second portion 102 including N stages of segments, the ends of each of the last stages of which are a plurality of end segments thereof, may be referred to as probes (e.g., deep probes or cortical flexible membranes), and the end segments thereof may be referred to as probe-implanted portions.
For the second part 102 including N-th-stage segments, a plurality of branches are branched from each of the nth-stage segments as N + 1-th-stage segments. In other words, the plurality of branches branched from the respective segments in the nth stage segment, i.e., the plurality of segments in the (n + 1) th stage segment. Therefore, the number of segments in the N +1 th-level segment is greater than the number of segments in the N-th-level segment, and the leads 12 formed in each of the N + 1-th-level segments are subsets of the leads 12 formed in the N-th-level segment, where N is an integer and 0 < N.
In the example of fig. 1, one of the second portions 102 comprises two levels of segmentation, a first level of segmentation 1023 and a second level of segmentation 1024, respectively, i.e. N equals 2. Wherein the first stage segments 1023 of the second portion 102 comprise one segment from which branches a plurality of branches to form a plurality of segments of the second stage segment 1024.
As shown in fig. 1 and 2, the plurality of lead wires 12 in the first-stage section 1023 are dispersed into each first-type end section 1021 of the second-stage section 1024, and are finally connected to each electrode 13 in each first-type end section 1021. Conversely, the leads 12 in each first type end section 1021 of the second stage section 1024 are collected in the first stage section 1023 and finally connected to the contact pads 11.
According to an embodiment of the present application, the second part adopts a multi-stage segmentation design, and the number of segments in each stage of segmentation is gradually increased from the first stage of segmentation to the nth stage of segmentation, so that the number of segments in the last stage of segmentation (nth stage of segmentation) can be much larger than the number of segments in the first stage of segmentation (for example, multiplied by number), and the end regions of the segments in the last stage of segmentation are set as probes. Therefore, the number of the probes of the brain electrode device is large, a large implantation range can be covered, and the detection area of a single brain electrode device can be increased. Furthermore, the number of brain electrode devices required by electroencephalogram signal detection can be reduced, the number of rear-end adapter interfaces connected with the brain electrode devices is reduced, and accordingly trauma to the skull of an implanted person is reduced.
In addition, the second part 102 adopts a multi-stage segmentation design, the number of segments in each stage of segmentation is gradually reduced according to the sequence from the Nth stage of segmentation to the first stage of segmentation, and the grouping management of the probes can be facilitated, so that the winding among multiple wires can be prevented.
According to some embodiments, the end sections of the second portion 102 comprising N-stage segments are configured as a first type end section 1021, and the end sections of the remaining second portion 102 are configured as a second type end section 1022.
The example of fig. 1 has two second portions 102, wherein one second portion 102 comprises multi-level segmentation and the other second portion 102 does not have multi-level segmentation. Second part 102 comprising multi-level segments is embodied as two-level segments, i.e. N equals 2, wherein the end segments of each of the second-level segments 1024 are configured as first-type end segments 1021, each first-type end segment 1021 being provided with a plurality of deep electrodes 1323 to serve as deep probes for detecting deep brain signals. The second portion 102, which does not have multi-stage segmentation, has its end section configured as a second type end section 1022 to serve as a cortical flexible membrane, detecting cortical regional brain signals.
It will be appreciated that the second type of end segment 1022, which acts as a cortical flexible membrane for attachment to the cortical surface, may each cover a larger surface of the brain region with a corresponding larger detection range of the brain region; the first type end section 1021 serving as a deep probe is used for implanting into a deep brain region, so that the deep brain region can be conveniently inserted and damaged, the deep probe is generally in a shape of a slender needle, and the detection range of the brain region which can be covered by each deep probe is small. Therefore, the number of deep probes for detecting deep electroencephalograms is generally far greater than the number of cortical flexible membranes required for detecting cortical electroencephalograms for the same brain region.
In one example, in the brain electrode apparatus 100, each cortical flexible membrane corresponds to a plurality of deep probes, i.e., each second-type end segment 1022 corresponds to a plurality of first-type end segments 1021, each second-type end segment 1022 has a plurality of through holes 10c disposed therein, the number of through holes 10c in each second-type end segment 1022 is equal to the number of first-type end segments 1021 corresponding to the second-type end segment 1022, and each first-type end segment 1021 is configured to pass through its corresponding through hole 10c and be inserted into deep brain tissue.
In this embodiment, the number of end segments of the second portion 102 including N-level segments is larger, the end segments of the second portion 102 including N-level segments are each configured as a first type end segment 1021, and the end segments of the second portion 102 not including N-level segments are configured as a second type end segment 1022. This may allow the number of first type end segments 1021 to be much larger than the number of second type end segments 1022, facilitating matching the number of first type end segments 1021 and the number of second type end segments 1022 required, and facilitating reducing the number of second portions 102 required for brain electrical signal detection, facilitating grouping management of probes.
According to some embodiments, the plurality of through holes 10c are distributed in an array in the second type end section 1022. Therefore, the detection distribution density and the distribution uniformity of the deep probe can be improved, and the acquisition, analysis and detection of deep electroencephalogram signals can be facilitated.
In the example of fig. 3, the second-type end section 1022 includes a plurality of columns of through holes 10c and a plurality of columns of electrodes, the plurality of columns of through holes 10c being alternately arranged with the plurality of columns of electrodes. Of course, fig. 3 is only one example of the form of the through holes 10c distributed in an array, and other embodiments are possible.
As shown in fig. 1 and 4, according to some embodiments, brain electrode device 200 further comprises a support substrate 15, the support substrate 15 having formed thereon a first portion 101 of flexible substrate 10. In one example, the support substrate 15 may be a silicon wafer. The first portion 101 of the flexible substrate 10 has an array of probe pads therein, and the first portion 101 is supported by a support substrate 15 to facilitate connection operations of the contact pads 11 of the array of probe pads to an external circuit, such as crimping or soldering operations.
According to some embodiments, the thickness of the sections of the plurality of second portions 102 other than the respective end sections is greater than the thickness of the respective end sections of the plurality of second portions 102.
In one example, the difference between the thickness of the sections of the plurality of second portions 102 other than the respective end sections and the thickness of the respective end sections of the plurality of second portions 102 may be 5 μm to 50 μm, for example, may be 5 μm, 10 μm, 20 μm, 30 μm, 40 μm, 50 μm.
In the brain electrode apparatus 100 illustrated in fig. 1, an end section of one second portion 102 is a first type end section 1021, a section of the second portion 102 other than the first type end section 1021 has a thickness greater than a thickness of the first type end section 1021, and an end section of the other second portion 102 is a second type end section 1022, and a section of the second portion 102 other than the second type end section 1022 has a thickness greater than a thickness of the second type end section 1022.
In the example of fig. 4, the sections of the second portion 102 other than the end section (second type end section 1022) have one more reinforcing layer 1000 relative to its end section (second type end section 10220), the thickness d of the reinforcing layer 1000 being 5 μm-50 μm.
The presence of the reinforcement layer 1000 may be advantageous. The end section of the second part 102 is used to form a probe, and it is required to have good flexibility to avoid damaging the brain, so its thickness should not be too large, and thickening the section of the second part 102 except the end section can enhance the strength and rigidity of the section, avoid the breakage and damage of the section, and help prevent the second parts 102 from being twisted.
As shown in fig. 1, according to some embodiments, the first type end section 1021 and/or the second type end section 1022 of the second portion 102 are reinforced by a biocompatible material.
Biocompatible materials are materials that can be removed, decomposed, and dissolved under the influence and action of biological tissues after being implanted into an organism. By way of example, and not limitation, the biocompatible material includes fibroin. The end segment of the second part 102 is wrapped with a fibroin solution, and after the fibroin solution is dried and cured, the hardness of the end segment of the second part 102 can be enhanced, thereby facilitating implantation into the brain of an organism. After the terminal section of the second part 102 is implanted into the brain of an organism, fibroin can be dissolved when meeting brain tissue fluid, so that the terminal section recovers the original flexibility, and the brain can be prevented from being damaged in the later electric signal acquisition process.
In one example, the first type end section 1021 of the second portion 102 is reinforced with fibroin to facilitate implantation into a deep brain region of an organism. After the first type end section 1021 is implanted into the deep brain region, fibroin dissolves and disappears when meeting brain tissue fluid, so that the first type end section 1021 recovers the original flexibility, and the deep brain region is prevented from being damaged in the later electric signal acquisition process.
Referring to fig. 5, fig. 5 is a schematic diagram illustrating an exploded structure of an electrode assembly 200 according to some embodiments of the present disclosure. As shown in fig. 5, the electrode device 200 includes the brain electrode device 100 according to any one of the above-described embodiments, and a data adapter 30.
The data bridge 30 is electrically connected to the plurality of contact pads 11 in the probe pad array, and is configured to transmit signals to the plurality of contact pads 11 or receive signals from the plurality of contact pads 11. In one example, the plurality of electrodes (depth electrodes 13 or cortical electrodes 14) of each end segment of the brain electrode device 100 acquire brain tissue signals and transmit the acquired signals to the data adapter 30 through the contact pads 11 and then to an external circuit, such as to a brain signal acquisition chip, through the data adapter 30. In one example, the external circuit transmits a signal to the brain electrode assembly 100 through the data adapter 30, which acts on the brain tissue through the electrodes (the depth electrodes 13 or the cortical electrodes 14) of the tip section of the brain electrode assembly 100 to output a stimulation signal to the brain tissue.
According to an embodiment of the present disclosure, electrode device 200 comprises brain electrode device 100. The brain electrode apparatus 100 includes both the first type of end section 1021 serving as a deep probe and the second type of end section 1022 serving as a cortical flexible membrane, and thus can detect brain signals at different depths within the brain tissue as well as brain signals at specific regions of the surface of the brain tissue. Also, a through hole is provided in the second type end section 1022 acting as a cortical flexible membrane through which the first type end section 1021 acting as a deep probe may pass for implantation in a deep brain region. Therefore, the cortical electroencephalogram signal and the deep electroencephalogram signal can be acquired simultaneously in the same brain area, namely, the deep brain signal and the cortical area brain signal in the same brain area can be acquired simultaneously, and the brain signal can be analyzed and detected conveniently.
As shown in fig. 5, according to some embodiments, the data switch 30 includes a pad array board 31 and a data interface board 32, and the pad array board 31 and the data interface board 32 are electrically connected.
The pad array board 31 includes a plurality of pads 311, and the plurality of pads 311 are electrically connected to a plurality of contact pads 11 in the probe pad array, respectively, to achieve electrical connection between the data adaptor 30 and the brain electrode device 100. In some embodiments, the pad array board 31 is a PCB board.
The data interface board 32 includes a plurality of electrical contacts electrically connected to the plurality of pads 311 of the pad array board 31, respectively. In some embodiments, the data interface board 32 serves as a chip interface terminal having a specific number (e.g., 4) of chip interfaces 320, each chip interface 320 having a plurality of electrical contacts therein, and a chip (e.g., a brain signal acquisition chip) can be inserted into the chip interface 320 to enable communication connection of the chip with the electrode device 200. In some embodiments, the data interface board 32 is a PCB board.
As shown in fig. 5, the data hub 30 further includes a flexible wiring board 33 according to some embodiments. The flexible wiring board 33 includes a plurality of cables 330, and the plurality of cables 330 electrically connect respective ones of the plurality of electrical contacts to respective ones 311 of the plurality of pads, respectively. In some embodiments, there is a one-to-one correspondence between electrical contacts, pads 311, and wires 330, each wire 330 electrically connecting a corresponding electrical contact to a corresponding pad 311. In some embodiments, the flexible wiring board 33 is a flexible PCB board.
The flexible wiring board 33 is used for connecting the pad array board 31 and the data interface board 32 to realize flexible transition of the pad array board 31 and the data interface board 32. In this way, a flexible arrangement of the position between the brain electrode apparatus 100 and the chip may be facilitated, e.g. the chip may be placed perpendicular with respect to the direction of probe implantation of the brain electrode apparatus 100.
Another aspect of the present disclosure provides an electronic device including the electrode assembly 200 as described above. The electronic device may include, but is not limited to, an implantable neural stimulator, an implantable neural recorder, an implantable stimulator-recorder, and the like.
Please refer to fig. 6 and 7. Fig. 6 is a flow chart of a method 400 for preparing a brain electrode device according to some embodiments of the present application. Fig. 7 is a schematic diagram of a process for preparing a brain electrode device according to some embodiments of the present application.
As shown in fig. 6, the method 400 includes the following steps.
In step 401, as shown in fig. 7 (b), a first flexible base layer 52 is formed on the support substrate 50. The first flexible substrate layer 52 comprises a first region located at a first end of the brain electrode apparatus and a plurality of second regions extending from the first region to a second end of the brain electrode apparatus, the second end being opposite the first end.
In step 402, as shown in (c) and (d) of fig. 7, a metal pattern layer is formed on the first flexible base layer 52. The metal pattern layer includes a probe pad array, a plurality of electrodes 501, and a plurality of leads. Wherein the probe pad array includes a plurality of contact pads 502, the plurality of contact pads 502 being formed on the first region. The plurality of electrodes 501 are formed in each end section of the plurality of second regions remote from the first region, the plurality of electrodes 501 including a plurality of deep electrodes formed in the first type end section and a plurality of cortical electrodes formed in the second type end section, and each end section of the plurality of second regions including the first type end section and the second type end section. A plurality of wires are formed on the plurality of second regions to electrically connect the respective electrodes 501 of the plurality of electrodes 501 to the respective contact pads 502 of the plurality of contact pads 502, respectively.
In step 403, as shown in fig. 7 (e), the second flexible base layer 53 is covered on the first flexible base layer 52 on which the metal pattern layer has been formed. The first and second flexible substrate layers 52, 53 together constitute a flexible substrate layer.
According to an embodiment of the present application, the plurality of second parts of the brain electrode apparatus comprise both the first type of end segment acting as a deep probe and the second type of end segment acting as a cortical flexible membrane, and thus the brain electrode apparatus can detect brain signals at different depths within the brain tissue as well as at specific areas of the surface of the brain tissue. Also, a through hole is provided in the second type of end section acting as a cortical flexible membrane through which the first type of end section acting as a deep probe may pass for implantation in the deep brain region. Therefore, the cortical electroencephalogram signal and the deep electroencephalogram signal can be acquired simultaneously in the same brain area, namely, the deep brain signal and the cortical area brain signal in the same brain area can be acquired simultaneously, and the brain signal can be analyzed and detected conveniently.
In addition, the through holes arranged on the second type end sections can also improve the stress of the second type end sections, improve the flexibility of the second type end sections and further be beneficial to improving the fitting property of the second type end sections and the surface of brain tissue.
According to some embodiments, forming a metal pattern layer on the first flexible substrate layer 52 (step 402) comprises the following steps.
First, as shown in (c) of fig. 7, a pattern of a plurality of electrodes 501 and a plurality of leads is prepared on the second region of the first flexible base layer 52 by an etching patterning process. Wherein the plurality of electrodes 501 comprises a plurality of deep electrodes and a plurality of cortical electrodes.
Next, as shown in (d) of fig. 7, a pattern of the probe pad array is prepared on the first region of the first flexible base layer 52 by an etching patterning process.
According to some embodiments, removing portions of the support substrate 50 other than the first support substrate portion 500 (step 405) comprises the following steps.
First, as shown in (a) in fig. 7, before the first flexible base layer 52 is formed, a sacrificial layer 51 is formed on a portion of the support substrate 50 other than the first support substrate portion 500. In some embodiments, the sacrificial layer 51 is made of metal aluminum (Al), which can increase the release speed of the sacrificial layer 51, and facilitate the peeling of the portion of the support substrate 50 other than the first support substrate portion 500 from the first flexible base layer 52.
Next, as shown in (j) and (k) of fig. 7, the sacrificial layer 51 is etched away so that the portion of the support substrate 50 other than the first support substrate portion 500 is separated from the first flexible base layer 52, and then the portion of the support substrate 50 other than the first support substrate portion 500 is removed, leaving only the first support substrate portion 500 of the support substrate 50 for supporting the first portion of the flexible base.
The first portion of the flexible base having the probe pad array therein, supported by the first support substrate portion 500 of the support substrate 50, may facilitate a connection operation of the contact pads 21 of the probe pad array with an external circuit. The respective second portions of the flexible base, which are unsupported by the support substrate 50, can be bent to extend to different areas of the brain so that the tip-segmented probes of the second portions can be implanted in different areas of the brain.
According to some embodiments, the method 400 of preparing a brain electrode apparatus further comprises the following steps. As shown in (j) of fig. 7, before removing portions of the support substrate 50 other than the first support substrate portion 500, the flexible base reinforcement layer 55 is formed on sections of the plurality of second portions other than the respective end sections. In one example, the thickness d of the reinforcement layer 55 is 5 μm to 50 μm.
The end section of the second part is used to form a probe, which requires good flexibility to avoid damage to the brain, and therefore should not be too thick. The section of the second part except the end section is thickened, so that the strength and the rigidity of the section can be enhanced, the section is prevented from being broken and damaged, and the winding of a plurality of second parts is prevented.
A specific example of a method 400 of making a brain electrode device is described in detail below in conjunction with fig. 7.
As shown in fig. 7 (a), a patterned sacrificial layer 51 is deposited on the support substrate 50. This step may include the following process:
1) Depositing metal aluminum (Al) on the support substrate 50 by using a metal sputtering method, wherein the thickness of the aluminum layer is 100nm-2 mu m;
2) Coating photoresist on the aluminum layer, and carrying out patterning treatment on the photoresist to form a region to be corroded;
3) Corroding the aluminum layer in the area to be corroded by using aluminum corrosive liquid (the aluminum layer covered by the photoresist is not corroded);
4) The residual photoresist is removed, leaving a patterned aluminum layer, i.e., a sacrificial layer.
As shown in fig. 7 (b), the first flexible substrate layer 52 is spin-coated on the patterned sacrificial layer, and the first flexible substrate layer 52 is cured by a vacuum oven with a stepwise temperature rise. For example, the material of the first flexible substrate layer 52 is Polyimide (PI), with a thickness of 1 μm to 10 μm and a maximum curing temperature of 380 ℃.
As shown in fig. 7 (c), the electrodes 501 and the leads are prepared on the first flexible base layer 52. This step may include the following process:
1) Coating photoresist, and carrying out patterning treatment on the photoresist to form an arrangement region of the electrode and the lead, wherein the arrangement region is positioned on the second region of the first flexible substrate layer 52;
2) Depositing titanium (Ti) and gold (Au) on the arrangement area of the electrode and the lead by using a metal evaporation method to form the electrode and the lead; the thicknesses of titanium (Ti) and gold (Au) are respectively 5nm =5nm-50nm and 50nm =50nm-500nm;
3) And stripping the photoresist by using acetone, removing the metal layer on the photoresist, and only leaving the electrodes and leads in the arrangement area after stripping, wherein the electrodes comprise deep electrodes and cortical electrodes.
As shown in fig. 7 (d), a contact pad 502 is prepared on the first flexible substrate layer 52, which is prepared in the same process as the electrode 501 and the lead wires, except that the contact pad 502 is disposed on the first region of the first flexible substrate layer 52, and the metal deposition layer includes three layers of Ti (Ti), nickel (Ni), and gold (Au), which have thicknesses of Ti =5nm to 50nm, ni =100nm to 1500nm, and Au =50nm to 500nm, respectively;
as shown in fig. 7 (e), the second flexible substrate layer 53 (i.e., the encapsulation layer) is prepared on the electrodes 501, the leads, and the contact pads 502, and the second flexible substrate layer 53 is cured by stepwise temperature rise using a vacuum oven. For example, the material of the second flexible substrate layer 53 is Polyimide (PI), with a thickness of 2 μm to 20 μm and a maximum curing temperature of 380 ℃. At this point, the electrodes, leads, and contact pads are all encapsulated within the flexible substrate layer.
As shown in fig. 7 (f), an aluminum hard mask (hardmark) layer 54 is formed on the second flexible base layer 53 by a sputtering process, and has a thickness of 50nm to 200nm.
As shown in (g) of fig. 7, the aluminum hard mask layer 54 is subjected to patterning processing. This step may include the following process:
1) Coating photoresist on the metal aluminum layer, and carrying out graphical treatment on the photoresist to form a region to be corroded;
2) Corroding the aluminum layer in the region to be corroded by using an aluminum corrosive liquid, wherein the aluminum layer of the part covered by the photoresist is not corroded;
3) The residual photoresist is removed, leaving a patterned aluminum layer for use as a mask layer for etching the first and second flexible substrate layers.
As shown in fig. 7 (h), the first flexible base layer 52 and the second flexible base layer 53 are etched using the patterned aluminum hard mask layer 54 as a mask. This step may include the following process:
etching the PI layers (the first flexible substrate layer 52 and the second flexible substrate layer 53) in the region to be etched (the region uncovered by the aluminum hard mask layer 54) by using a deep silicon etching technology, wherein the lateral erosion single side of the PI layer etching is +/-0.5 um;
after the PI layer is etched, the first portions and the respective second portions may be patterned, and the connection hole 50b exposing the electrode 501, the contact hole 50a exposing the contact pad 502, and the via hole 50c penetrating the PI layer may be formed.
Removing the patterned aluminum hard mask layer 54 by using an aluminum etchant, and the structure after removing the aluminum hard mask layer 54 is shown in (i) of fig. 7;
as shown in (j) of fig. 7, a reinforcement layer 55 is formed on the sections of the respective second portions of the flexible substrate except for the end sections, using spin coating and photolithography patterning techniques again, the material of the reinforcement layer 55 being Polyimide (PI) having a thickness of 5 μm to 50 μm. The process of the photolithographic patterning technology of the reinforcement layer may refer to the photolithographic process of the flexible substrate layer, which is not described herein again.
As shown in (j) of fig. 7, the sacrificial layer 51 is etched with an etching liquid, and a corresponding support substrate portion of the sacrificial layer 51 is removed, leaving only the first support substrate portion 500 for supporting the first portion of the flexible base,
the structure after removing the portion of the support substrate corresponding to the sacrificial layer 51 is shown in (k) of fig. 7.
It should be noted that the above preparation steps are only illustrative of the preparation method 400, and the preparation method 400 is not limited to the above examples, and can be specifically adjusted according to actual process requirements.
It can be understood that the brain electrode device and the manufacturing method thereof according to the embodiments of the present disclosure are based on the same inventive concept, and thus the manufacturing method according to the embodiments of the present disclosure also has the same or similar beneficial effects as the brain electrode device described above, and will not be described herein again.
The above embodiments are only used to illustrate the technical solutions of the present application, and not to limit the same. In particular, the technical features mentioned in the embodiments can be combined in any way as long as there is no structural conflict. The present application is not intended to be limited to the particular embodiments disclosed herein but is to cover all embodiments that may fall within the scope of the appended claims.
Claims (12)
1. A brain electrode apparatus comprising:
a flexible substrate comprising a first portion at a first end of the brain electrode apparatus and a plurality of second portions extending from the first portion to a second end of the brain electrode apparatus, the second end being opposite the first end;
a probe pad array comprising a plurality of contact pads formed in the first portion;
a plurality of deep electrodes and a plurality of cortical electrodes formed in respective end segments of the plurality of second portions distal from the first portion; and
a plurality of leads formed in the plurality of second portions to electrically connect respective ones of the plurality of deep electrodes and the plurality of cortical electrodes to respective ones of the plurality of contact pads, respectively,
wherein each end segment of the plurality of second portions comprises a first type end segment that serves as a deep probe for implantation into a deep brain region of the organism in which the plurality of deep electrodes are formed,
wherein each end section of the plurality of second portions further comprises a second type of end section that acts as a cortical flexible membrane for placement on a cortical surface of the organism in which the plurality of cortical electrodes are formed, and
wherein the second type of end section is provided with a plurality of through holes through the flexible substrate, each through hole being dimensioned to allow one or more corresponding first type of end sections to pass through.
2. The brain electrode apparatus of claim 1,
wherein at least one of the plurality of second portions comprises N stages of segmentation, the N stages of segmentation being sequentially arranged in a direction from the first end to the second end, and the Nth stage of segmentation of the at least one second portion comprises each end segment of the at least one second portion, wherein N is an integer greater than or equal to 2, and
wherein a plurality of branches are branched from each of nth-stage segments as an N +1 th-stage segment, and leads formed in each of the N +1 th-stage segments are subsets of leads formed in the nth-stage segment, where N is an integer and 0 < N < N.
3. The brain electrode apparatus of claim 2 wherein the end segments of the at least one second portion comprising N-stage segments are configured as a first type of end segment and the end segments of the remaining second portions are configured as a second type of end segment.
4. The brain electrode apparatus according to claim 1 wherein the plurality of through holes are distributed in an array in the second type of tip section.
5. The brain electrode apparatus of claim 1 further comprising: a support substrate on which the first portion of the flexible base is formed.
6. The brain electrode apparatus of claim 1 wherein the thickness of the sections of the second portions other than the end sections is greater than the thickness of the end sections of the second portions.
7. The brain electrode apparatus according to any one of claims 1 to 6, wherein the first type of end segment and/or the second type of end segment is reinforced by a biocompatible material to facilitate implantation into the brain of an organism.
8. The brain electrode device of claim 7, wherein the biocompatible material comprises fibroin.
9. An electrode device, comprising:
the brain electrode device of any one of claims 1 to 8; and
a data adapter electrically connected to the plurality of contact pads in the probe pad array, configured to transmit signals to or receive signals from the plurality of contact pads.
10. An electronic device comprising an electrode arrangement as claimed in claim 9.
11. A method of making a brain electrode device, the method comprising:
forming a first flexible base layer on a support substrate, the first flexible base layer comprising a first region at a first end of the brain electrode apparatus and a plurality of second regions extending from the first region to a second end of the brain electrode apparatus, the second end being opposite the first end;
forming a metal pattern layer on the first flexible base layer, the metal pattern layer including a probe pad array, a plurality of deep electrodes, a plurality of skin electrodes, and a plurality of leads, wherein the probe pad array includes a plurality of contact pads formed on the first region, the plurality of deep electrodes and the plurality of skin electrodes are formed in respective end sections of the plurality of second regions remote from the first region, and wherein the respective end sections of the plurality of second regions include first type end sections in which the plurality of deep electrodes are formed and second type end sections in which the plurality of skin electrodes are formed, and the plurality of leads are formed on the plurality of second regions to electrically connect respective ones of the plurality of deep electrodes and the plurality of skin electrodes to respective ones of the plurality of contact pads, respectively;
covering a second flexible substrate layer on the first flexible substrate layer on which the metal pattern layer has been formed;
etching the second flexible base layer and the first flexible base layer to expose the plurality of contact pads, the plurality of deep electrodes, and the plurality of cortical electrodes, forming a first portion corresponding to the pattern of the first region and a plurality of second portions corresponding to the pattern of the plurality of second regions, and etching a plurality of through-holes through the second flexible base layer and the first flexible base layer in second-type end sections of the plurality of second portions, wherein each through-hole is sized to allow one or more first-type end sections of the plurality of second portions to pass therethrough; and
removing a portion of the support substrate other than a first support substrate portion, the first support substrate portion corresponding to the first portion.
12. The method of claim 11, further comprising:
forming a flexible base reinforcement layer on sections of the plurality of second portions other than the respective end sections before removing portions of the support substrate other than the first support substrate portion.
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| CN202211054186.XA CN115381458A (en) | 2022-08-31 | 2022-08-31 | Brain electrode device, preparation method thereof, electrode device and electronic equipment |
| PCT/CN2023/114466 WO2024046186A1 (en) | 2022-08-31 | 2023-08-23 | Brain electrode apparatus, preparation method therefor, electrode apparatus, and electronic device |
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| CN202211054186.XA CN115381458A (en) | 2022-08-31 | 2022-08-31 | Brain electrode device, preparation method thereof, electrode device and electronic equipment |
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