Neural electrode with drug delivery capability and preparation method thereof

Abstract

The invention discloses a neural electrode with drug delivery capability and a preparation method thereof, the neural electrode comprises an electrode main body, the intervention end of the electrode main body is provided with a plurality of electrical detection points, the electrical detection points are located at the first side of the electrode main body, and the connection end of the electrode main body is provided with a lead-out bonding pad; the micro-channel is arranged on the second side of the electrode main body, the front end of the micro-channel extends to the intervention end of the electrode main body and can intervene into the tissue along with the intervention end, a channel outlet is formed in the front end of the micro-channel, and a channel inlet is formed in the rear end of the micro-channel. According to the invention, the technical effects that the drug delivery to the implanted electrode area is more convenient, and as injection equipment for drug delivery only needs to be in butt joint with the inlet of the runner and does not need to intervene into the tissue, the damage to the tissue is reduced, and even if the drug needs to be delivered frequently, the damage to the tissue can be better reduced are achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical equipment, and in particular to a neural electrode with drug delivery capability and a preparation method thereof. Background Art

[0002] In neuroscience research, electrodes are one of the most core research methods, which can directly reflect the state and functional connection of nerves by recording the electrical activity of the nervous system. At the same time, many experiments require the delivery of drugs to the entire central nervous system or even to specific areas to assist in the study of neural function or verify the function of drugs.

[0003] Due to the existence of the blood-brain barrier, its blocking phenomenon makes it difficult to achieve good drug delivery to the central nervous system through oral or intravenous injection, let alone delivery to specific areas. Therefore, the method currently used in experiments is a microinjection device combined with a stereotaxic instrument. After positioning, the syringe is directly inserted and microinjection is performed.

[0004] However, during the entire experimental process, it is difficult to perform drug injection surgery in the electrode implantation area, and microinjection often needs to be performed multiple times. Frequent use of syringes can cause great harm to experimental animals and may affect the experimental results. Summary of the invention

[0005] The main purpose of the present invention is to provide a neural electrode with drug delivery capability to solve the problems in the related art that it is difficult to perform drug injection surgery in the electrode implantation area and that frequent use of syringes causes great harm to experimental animals.

[0006] In order to achieve the above object, the present invention provides a neural electrode with drug delivery capability, comprising:

[0007] An electrode body, wherein the intervention end of the electrode body is provided with a plurality of electrical detection points, the electrical detection points are located on a first side of the electrode body, and the connection end of the electrode body is provided with a lead-out pad;

[0008] The microfluidic channel is arranged on the second side of the electrode body, the front end of the microfluidic channel extends to the intervention end of the electrode body and can intervene in the tissue along the intervention end, the front end of the microfluidic channel is provided with a channel outlet, and the rear end of the microfluidic channel is provided with a channel inlet.

[0009] Furthermore, the neural electrode also includes an adapter, the connection end of the electrode body is provided with a lead-out pad, the adapter is electrically connected to the lead-out pad, and the adapter is used to be electrically connected to the detection device.

[0010] Furthermore, the electrode body includes a substrate, a metal wiring, an insulating layer and a supporting layer, wherein the substrate and the insulating layer are made of biocompatible materials, the metal wiring is arranged on the substrate, the insulating layer covers the metal wiring, and the supporting layer covers the insulating layer;

[0011] A plurality of electrical detection points are arranged on the substrate, and a partial area of ​​the metal wiring is exposed through the electrical detection points, and a rear end of the metal wiring is exposed on the substrate to form the lead pad;

[0012] The microchannel is arranged on the supporting layer.

[0013] Furthermore, the metal wiring includes a first metal layer, a second metal layer and a third metal layer stacked in sequence on the substrate, the area on the first metal layer corresponding to the detection hole and the lead-out pad is selectively removed, and a partial area of ​​the second metal layer is exposed through the electrical detection point; the first metal layer is titanium, the second metal layer is platinum, and the third metal layer is gold.

[0014] Furthermore, the material of the support layer is nickel.

[0015] Furthermore, the rear end of the substrate includes a connecting portion and an extension portion connected in sequence, the rear end of the metal wiring extends to the extension portion after passing through the connecting portion, and the lead pad includes the extension portion and the metal wiring located on the extension portion;

[0016] The rear end of the insulating layer covers the metal wiring located at the connecting portion, and the rear end of the supporting layer covers the insulating layer corresponding to the connecting portion.

[0017] Furthermore, the neural electrode also includes a reinforcement beam and a connecting tube, wherein the reinforcement beam is arranged at a position corresponding to the support layer and the connecting portion, and the connecting tube is arranged on the reinforcement beam, and the rear end of the microchannel passes through and is connected to the lower end of the connecting tube.

[0018] Furthermore, the support layer, the reinforcement beam, the connecting pipe and the microfluidic channel are conformally coated with a protective layer, and the protective layer is made of a biocompatible material.

[0019] Furthermore, the adapter includes an adapter circuit board, an adapter plug board and a cable pad, the adapter plug board and the cable pad are electrically connected to the first end and the second end of the adapter circuit board respectively, and multiple interfaces are provided at both ends of the adapter plug board, and the cable pad is electrically connected to the lead-out pad.

[0020] Furthermore, the lead pad and the wiring pad are arranged vertically opposite to each other, and the lead pad and the wiring pad are electrically connected through an anisotropic conductive film, so that the metal wiring on the lead pad is electrically interconnected with the wiring pad in a vertical direction.

[0021] Furthermore, the neural electrode also includes an electrode shell, the adapter plate is fixedly arranged in the electrode shell, and an electrode support platform is arranged on the electrode shell, and the electrode support platform plays a supporting role for the rear end of the electrode body.

[0022] Further, the electrode housing includes a first fixed housing and a second fixed housing;

[0023] The first fixed housing is provided with limited side walls on both sides, the adapter circuit board is arranged on the first fixed housing and is located between the limited side walls on both sides, the electrode support platform is arranged on the first fixed housing, and the height of the electrode support platform is the same as the thickness of the adapter circuit board;

[0024] The second fixed shell is detachably fixed to the first fixed shell, and a pressing beam is arranged on the inner side of the second fixed shell, and the pressing beam is pressed on the adapter circuit board.

[0025] Further, a tube fixing structure is provided at the upper end of the second fixed housing;

[0026] The neural electrode also includes a rubber tube, a connecting thin tube and a connecting column, wherein the connecting thin tube is an L-shaped tube; the rubber tube is detachably fixedly connected to the tube fixing structure, the first end of the connecting thin tube is fixedly connected to the rubber tube, the second end of the connecting thin tube is fixedly connected to the connecting column, and the lower end of the connecting column is sleeved and fixed on the connecting tube.

[0027] Furthermore, a positioning column is provided on the first fixed shell, and a positioning hole is provided on the adapter circuit board, and the positioning hole is plugged and matched with the positioning column.

[0028] According to another aspect of the present invention, a method for preparing a neural electrode is provided, which is used to prepare the above-mentioned neural electrode. The method for preparing a neural electrode comprises the following steps:

[0029] preparing an electrode layer;

[0030] The microchannel is formed on the surface of the electrode layer by 3D printing;

[0031] The electrode layer is processed to obtain the electrode body conforming to the designed shape.

[0032] Further, preparing the electrode layer includes:

[0033] depositing a sacrificial layer on the substrate;

[0034] forming a bottom layer on the sacrificial layer using a biocompatible material;

[0035] The bottom layer is patterned using a photolithography process;

[0036] Using photolithography and metal deposition processes to form metal wiring on the bottom layer;

[0037] An insulating intermediate layer is formed on the bottom layer using a biocompatible material, and the rear end of the metal wiring is exposed on the bottom layer to form a lead pad.

[0038] Furthermore, preparing the electrode layer also includes:

[0039] A supporting layer with supporting properties is formed on the intermediate layer by adopting a photolithography process and a deposition process, and the supporting layer is patterned.

[0040] Furthermore, the electrode layer is processed to obtain the electrode body conforming to the designed shape, comprising:

[0041] A deposition process is used to form a protective layer on the microfluidic channel and the support layer;

[0042] Cut the protective layer and the middle layer according to the designed shape;

[0043] separating the bottom layer from the sacrificial layer;

[0044] An electrical detection point is formed on the first side of the electrode body.

[0045] Furthermore, the method further comprises the following steps:

[0046] Electrically connect the adapter to the lead pad;

[0047] Install the adapter into the electrode housing and connect the flow channel inlet of the microfluidic channel to the tube assembly;

[0048] Secure the tube assembly to the electrode housing.

[0049] In the embodiment of the present invention, an electrode body is provided, and the intervention end of the electrode body is provided with a plurality of electrical detection points, and the electrical detection points are located on the first side of the electrode body, and the connection end of the electrode body is provided with a lead pad; a microfluidic channel is provided on the second side of the electrode body, and the front end of the microfluidic channel extends to the intervention end of the electrode body and can be inserted into the tissue with the intervention end, the front end of the microfluidic channel is provided with a channel outlet, and the rear end of the microfluidic channel is provided with a channel inlet; an adapter, the adapter is electrically connected to the lead pad, and the adapter is used to be electrically connected to the detection device. In the present invention, the front end of the microfluidic channel can be inserted into the tissue with the intervention end of the electrode body, and the rear end of the microfluidic channel is close to the rear end of the electrode body. After the neural electrode is implanted in the tissue, the flow channel outlet of the microfluidic channel remains inside the tissue, and the flow channel inlet remains outside the tissue. Drugs can be delivered to the tissue through the microfluidic channel, making it more convenient to deliver drugs to the implanted electrode area. In addition, since the drug delivery injection device only needs to dock with the flow channel inlet and does not need to intervene in the tissue, damage to the tissue is reduced. Even if frequent drug delivery is required, the damage to the tissue can be better reduced, thereby solving the problem in related technologies that it is difficult to perform drug injection surgery in the implanted electrode area and that frequent use of syringes causes great harm to experimental animals. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention, so that other features, purposes and advantages of the present invention become more obvious. The accompanying drawings of the exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the accompanying drawings:

[0051] Figure 1 is a schematic diagram of the structure after the micro-channel and the electrode body are combined according to an embodiment of the present invention;

[0052] Figure 2 yes Figure 1 A side view schematic diagram of the structure;

[0053] Figure 3 is a schematic diagram of a top view of the structure of an electrode body according to an embodiment of the present invention;

[0054] Figure 4 is a schematic diagram of the side structure of the electrode body according to an embodiment of the present invention;

[0055] Figure 5 is a schematic diagram of an enlarged structure of the tip of an electrode body according to an embodiment of the present invention;

[0056] Figure 6 is a schematic diagram of a multi-layer structure of metal wiring according to an embodiment of the present invention;

[0057] Figure 7is a schematic structural diagram of a transition piece according to an embodiment of the present invention;

[0058] Figure 8 is a schematic diagram of electrical connection between the wiring pad of the adapter and the lead-out pad of the electrode body according to an embodiment of the present invention;

[0059] Fig. 9 is a schematic diagram of the structure of installing an electrode housing according to an embodiment of the present invention;

[0060] Fig.10 yes Fig. 9 Schematic diagram of the explosion structure;

[0061] Fig.11 is a schematic structural diagram of a second fixed housing according to an embodiment of the present invention;

[0062] Among them, 1 electrode body, 10 substrate, 101 extension part, 102 connection part, 11 metal wiring, 110 first metal layer, 111 second metal layer, 112 third metal layer, 12 electrical detection point, 13 insulation layer, 14 support layer, 2 microchannel, 20 channel outlet, 3 reinforcement beam, 4 connecting column, 5 lead pad, 6 adapter, 60 adapter circuit board, 600 positioning hole, 61 adapter plug board, 610 interface, 62 wiring pad, 7 anisotropic conductive film, 8 electrode shell, 80 first fixed shell, 800 electrode support platform, 801 limiting side wall, 802 positioning column, 810 buckle, 811 tube fixing structure, 812 clamping beam, 81 second fixed shell, 9 tube assembly, 90 connecting tube, 91 connecting thin tube, 92 rubber tube. DETAILED DESCRIPTION

[0063] In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0064] It should be noted that the terms "first", "second", etc. in the specification and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the numbers used in this way can be interchanged under appropriate circumstances to facilitate the embodiments of the present invention described herein.

[0065] In the present invention, the directions or positional relationships indicated by the terms "upper", "lower", "inner", etc. are based on the directions or positional relationships shown in the drawings. These terms are mainly used to better describe the present invention and its embodiments, and are not used to limit the indicated devices, elements or components to have a specific direction, or to be constructed and operated in a specific direction.

[0066] In addition, some of the above terms may be used to express other meanings in addition to indicating orientation or positional relationship. For example, the term "on" may also be used to express a certain dependency or connection relationship in some cases. For those skilled in the art, the specific meanings of these terms in the present invention can be understood according to specific circumstances.

[0067] In addition, the terms "disposed", "provided with", "connected", "fixed" and the like should be understood in a broad sense. For example, "connected" can be a fixed connection, a detachable connection, or an integral structure; it can be a mechanical connection, or an electrical connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be an internal connection between two devices, elements or components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0068] In addition, the term "plurality" shall mean two or more.

[0069] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0070] To solve relevant technical problems, such as Figures 1 to 4 As shown, an embodiment of the present invention provides a neural electrode with drug delivery capability, comprising:

[0071] An electrode body 1, wherein a plurality of electrical detection points 12 are arranged at the intervention end of the electrode body 1, and the electrical detection points 12 are located at a first side of the electrode body 1, and a lead-out pad 5 is arranged at the connection end of the electrode body 1;

[0072] The microfluidic channel 2 is arranged on the second side of the electrode body 1. The front end of the microfluidic channel 2 extends to the intervention end of the electrode body 1 and can intervene in the tissue along the intervention end. The front end of the microfluidic channel 2 is provided with a channel outlet 20, and the rear end of the microfluidic channel 2 is provided with a channel inlet.

[0073] In this embodiment, the intervention end of the electrode body 1 is an elongated structure, so that it can be inserted into the tissue, such as the inside of the animal brain tissue. The rear end of the electrode body 1 is located outside the tissue, and it needs to be electrically connected to the detection device to transmit the electrical signal to the detection device. Therefore, the rear end of the electrode body 1 can be a wider structure, so as to facilitate the connection with the detection device. In this embodiment, the intervention end of the electrode body 1 is provided with a plurality of electrical detection points 12, and the electrical detection points 12 are located on the first side of the electrode body 1. The plurality of electrical detection points 12 can be distributed along the length direction of the electrode body 1. After the intervention end is inserted into the tissue, the electrical detection points 12 at different positions can perform signal detection at different positions in the tissue. The rear end of the electrode body 1 is a connection end, and a lead-out pad 5 is provided at the connection end. On the lead-out pad 5, the metal part of the electrode body 1 used for transmitting the signal is exposed to the outside, so as to facilitate the transmission of the signal to the outside.

[0074] On this basis, in this embodiment, a microfluidic channel 2 is provided on the electrode body 1, and the microfluidic channel 2 is a slender channel structure, so that it can enter the tissue with the intervention end of the electrode body 1. In order to avoid interference between the microfluidic channel 2 and the electrical detection point 12, the microfluidic channel 2 is arranged on the second side of the electrode body 1. It should be noted that the first side and the second side of the electrode body 1 can be two opposite sides of the electrode body 1, respectively, and sufficient layout space can be provided for the electrode body 1 with a flat intervention end. The front end opening of the microfluidic channel 2 forms a channel outlet 20, and the rear end opening of the microfluidic channel 2 forms a channel inlet. After the electrode body 1 intervenes in the tissue, the channel outlet 20 is located in the tissue, and the channel inlet is located outside the tissue. The injection device can be docked to the channel inlet, and the medicine is injected into the microfluidic channel 2 through the channel inlet, and the medicine then flows out through the channel outlet 20 into the vicinity of the electrode implantation area.

[0075] In this embodiment, the front end of the microfluidic channel 2 can be inserted into the tissue along with the intervention end of the electrode body 1, and the rear end of the microfluidic channel 2 is close to the rear end of the electrode body 1. After the neural electrode is implanted in the tissue, the flow channel outlet 20 of the microfluidic channel 2 remains inside the tissue, and the flow channel inlet remains outside the tissue. Drugs can be delivered to the tissue through the microfluidic channel 2, making it more convenient to deliver drugs to the implanted electrode area. In addition, since the injection device for drug delivery only needs to dock with the flow channel inlet and does not need to be inserted into the tissue, the damage to the tissue is reduced. Even if frequent drug delivery is required, the damage to the tissue can be better reduced, thereby solving the problem in the related art that it is difficult to perform drug injection surgery in the implanted electrode area, and the frequent use of syringes causes great harm to experimental animals.

[0076] In one embodiment, the microchannel 2 is a hollow tubular structure with an inner diameter of less than 100 micrometers. To reduce resistance during implantation, the channel outlet 20 at the front end of the microchannel 2 may be a 45° beveled section.

[0077] In one embodiment of the electrode body 1, Figures 3 to 6 As shown, the electrode body 1 includes a substrate 10, a metal wiring 11, an insulating layer 13 and a supporting layer 14. The substrate 10 and the insulating layer 13 are made of biocompatible materials. The metal wiring 11 is arranged on the substrate 10, the insulating layer 13 covers the metal wiring 11, and the supporting layer 14 covers the insulating layer 13;

[0078] A plurality of electrical detection points 12 are provided on the substrate 10, and a partial area of ​​the metal wiring 11 is exposed through the electrical detection points 12. The rear end of the metal wiring 11 is exposed on the substrate 10 and forms a lead pad 5;

[0079] The microchannel 2 is disposed on the support layer 14 .

[0080] Specifically, in order to solve the problem that the biocompatibility of neural electrodes in the related art is poor and is prone to cause biological immune reactions during long-term implantation, the substrate 10 and the insulating layer 13 of the electrode body 1 in this embodiment are made of biocompatible materials. For example, the substrate 10 is made of polyimide, so that the bottom of the electrode body 1 is insulated and has excellent biocompatibility, and the substrate 10 made of this material has good adhesion to the metal wiring. The portion of the substrate 10 corresponding to the intervention end can be etched to form an electrical detection point 12, and the rear end of the substrate 10 can be etched to form the shape of the lead pad 5, and the metal wiring 11 at these positions will be exposed to achieve the reception and transmission of neural electrophysiological signals.

[0081] The metal wiring 11 is the second layer of the entire electrode body 1. The metal wiring 11 is arranged on the substrate 10, and the overall thickness can be about 100 nanometers. It plays the role of connecting the electrical detection sites 2 of each channel of the electrode to the lead-out pads 54 one by one. The metal wiring 11 can be prepared by photolithography and deposition processes, so as to form multiple high-precision signal channels, and different signal channels correspond to different electrical detection points 12.

[0082] In one embodiment, Figure 6 As shown, the metal wiring 11 includes a first metal layer 110, a second metal layer 111 and a third metal layer 112 which are stacked in sequence on the substrate 10. The area on the first metal layer 110 corresponding to the detection hole and the lead-out pad 5 is selectively removed, and a partial area of ​​the second metal layer 111 is exposed through the electrical detection point 12; the first metal layer 110 is titanium, the second metal layer 111 is platinum, and the third metal layer 112 is gold.

[0083] Specifically, in the present embodiment, the metal used in the metal wiring 11 is a three-layer structure, which includes, from bottom to top, a first metal layer 110 of titanium material, a second metal layer 111 of platinum material, and a third metal layer 112 of gold material. The first metal layer 110 serves as an adhesion layer for the second metal layer 111. At the electrical detection site and the position where the metal wiring 11 is exposed by the lead-out pad 5, the first metal layer 110 will be selectively removed to enable the second metal layer 111 to become the metal that actually contacts the nerve tissue. The reason is that the second metal layer 111 is made of platinum material, and the interface of platinum has a lower electrochemical impedance, which can have a higher signal-to-noise ratio when collecting electrophysiological signals. The top layer of the third metal layer 112 made of gold material plays a role in reducing the resistance of the metal wiring 11 itself, and its good ductility can enable the metal wiring 11 to still be electrically conductive even with a certain degree of bending.

[0084] In one embodiment, the overall thickness of the metal wiring 11 is about 100 nanometers, wherein the thickness of the first metal layer 110 is 10 nanometers, the thickness of the second metal layer 111 is about 50 nanometers, and the thickness of the third metal layer 112 is about 50 nanometers.

[0085] The insulating layer 13 is the third layer of the entire electrode body 1. The insulating layer 13 can be made of polyimide or polyparaxylene, preferably polyparaxylene. The insulating layer 13 completely covers the metal wiring 11 to prevent the metal wiring 11 from contacting with the liquid in the body and being short-circuited. Polyparaxylene is a material with good biosafety, which is safe and reliable. In one embodiment, the thickness of the insulating layer 13 can be about 2 microns.

[0086] The support layer 14 is the fourth layer of the entire electrode body 1. The support layer 14 is made of a material with support properties, such as nickel. The support layer 14 increases the rigidity of the intervention end of the electrode body 1 so that it can be better inserted into the tissue. At the same time, the support layer 14 also has good toughness after using nickel, and will not break under large angle bending, which greatly reduces the risk of electrode breakage during surgery. In one embodiment, the thickness of the support layer 14 is about 15 to 20 microns.

[0087] It should be noted that the front end of the electrode body 1 needs to be inserted into the tissue, so it is designed to be a slender structure, while the rear end needs to be connected to the adapter 6, so it is designed to be a wider structure. Figure 1 and Figure 3 As shown, in this embodiment, the rear end of the substrate 10 includes a connecting portion 102 and an extension portion 101 connected in sequence, the rear end of the metal wiring 11 extends to the extension portion 101 after passing through the connecting portion 102, and the lead pad 5 includes the extension portion 101 and the metal wiring 11 located on the extension portion 101;

[0088] The rear end of the insulating layer 13 covers the metal wiring 11 located at the connecting portion 102 , and the rear end of the supporting layer 14 covers the insulating layer 13 corresponding to the connecting portion 102 .

[0089] Specifically, the connecting portion 102 in this embodiment is used to connect the wider extension portion 101 and the narrower front end portion on the electrode body 1, and the width of the connecting portion 102 is gradually changed. In one embodiment, the connecting portion 102 is triangular, and the strength of the mutation point between the front end portion and the rear end portion can be increased by setting the connecting portion 102, so as to avoid deformation or breakage of the front end portion of the electrode body 1. The wider extension portion 101 can be set as a square, and the extension portion 101 mainly includes a substrate 10 and a metal wiring 11 located on the substrate 10. The substrate 10 and the metal wiring 11 of this part naturally form the lead-out pad 5 of the electrode body. Therefore, the rear end of the insulating layer 13 only covers the metal wiring 11 of the connecting portion 102, and similarly, the rear end of the supporting layer 14 also only covers the insulating layer 13 corresponding to the connecting portion 102. In other words, the electrode body 1 still needs to maintain insulation performance and certain support performance in the area corresponding to the connecting portion 102, and only exposes the metal wiring 11 at the position corresponding to the extension portion 101 for electrical connection with the adapter 6.

[0090] In one embodiment, if Figure 1 and Figure 2 As shown, the neural electrode also includes a reinforcement beam 3 and a connecting column 4. The reinforcement beam 3 is arranged at a position corresponding to the support layer 14 and the connecting portion 102. The connecting column 4 is arranged on the reinforcement beam 3. The rear end of the microchannel 2 passes through and is connected to the lower end of the connecting column 4.

[0091] Specifically, in the present embodiment, since the microchannel 2 is also an elongated structure, in order to facilitate the injection of medicine into the microchannel 2, a connecting column 4 with a larger diameter needs to be provided at the rear end of the microchannel 2. After the connecting column 4 is provided, there is a sudden change in diameter at the connection position between the connecting column 4 and the microchannel 2, resulting in a decrease in structural strength. To this end, in the present embodiment, a reinforcing beam 3 is first provided at a position corresponding to the supporting layer 14 and the connecting portion 102, the rear end of the microchannel 2 extends into the reinforcing beam 3, and the lower end of the connecting column 4 is connected to the flow channel inlet of the microchannel 2. The provision of the reinforcing beam 3 can increase the strength of the microchannel 2 to the connecting column 4 at the sudden change in size, which can improve the yield and provide a stable drug delivery capability during preparation.

[0092] In one embodiment, the connecting column 4 is a hollow cylinder with a height of 2 mm and an outer diameter of 1 mm. The connecting column 4 may be perpendicular to the surface of the supporting layer 14 .

[0093] To further improve the biocompatibility of the entire neural electrode, in this embodiment, a protective layer (not shown in the figure) is conformally coated on the support layer 14, the reinforcement beam 3, the connecting column 4 and the microfluidic channel 2, and the protective layer is made of a biocompatible material. In one embodiment, the protective layer can be made of polyparaxylene.

[0094] To facilitate the connection between neural electrodes and detection equipment, such as Figure 7 and Figure 8 As shown, the neural electrode further includes an adapter 6, which is electrically connected to the lead pad 5, and the adapter 6 is also used to be electrically connected to the detection device.

[0095] In one embodiment of the adapter 6, the adapter 6 includes an adapter circuit board 60, an adapter plug board 61 and a cable pad 62, the adapter plug board 61 and the cable pad 62 are electrically connected to the first end and the second end of the adapter circuit board 60 respectively, and multiple interfaces 610 are provided at both ends of the adapter plug board 61, and the cable pad 62 is electrically connected to the lead-out pad 5.

[0096] Specifically, in this embodiment, the two ends of the adapter board 61 have multiple interfaces 610, which can all be Omnetics interfaces 610. The adapter board 61 and the adapter circuit board 60 can be welded and fixed, and the Omnetics interface 610 is a universal interface 610 of various neural electrophysiological signal detection devices at present, so the adapter board 61 can be compatible with various devices, and a single interface 610 supports at most electrical channels, and the Omnetics interface 610 on it can achieve a very reliable connection with the Omnetics pin interface 610 on the detection device.

[0097] The wiring pad 62 is welded and fixed to the other end of the adapter circuit board 60, and the wiring pad 62 can be electrically connected to the lead pad 5 at the rear end of the electrode body 1. In one embodiment, the wiring pad 62 is about 3 mm long and 100 μm wide, which is the same or close to the size of the lead pad 5.

[0098] To achieve electrical connection between the wiring pad 62 and the lead pad 5, as shown in FIG. Figure 8 As shown, in this embodiment, the lead pad 5 and the wiring pad 62 are arranged opposite to each other in the upper and lower directions, and the lead pad 5 and the wiring pad 62 are electrically connected through the anisotropic conductive film 7, so that the metal wiring 11 on the lead pad 5 and the wiring pad 62 are electrically interconnected in the vertical direction.

[0099] Specifically, in this embodiment, the anisotropic conductive film 7 enables the wiring pad 62 and the lead pad 5 to be electrically interconnected in the vertical direction under the action of heat and pressure, while still maintaining an insulation state in the horizontal direction, so that each channel on the electrode can be connected to the circuit on the adapter circuit board 60 in a one-to-one correspondence. After the anisotropic conductive film 7 is fixed on the wiring pad 62, the lead pad 5 and the wiring pad 62 are aligned under a microscope, and finally a hot press is used to make the two electrically conductive in the vertical direction.

[0100] In one embodiment, Fig. 9 As shown, the neural electrode further includes an electrode shell 8, the adapter plate is fixedly arranged in the electrode shell 8, and an electrode support platform 800 is arranged on the electrode shell 8, and the electrode support platform 800 supports the rear end of the electrode body 1.

[0101] Specifically, in this embodiment, the electrode shell 8 supports and protects the rear end of the adapter plate and the electrode body 1. After implantation, the electrode shell 8 is located outside the tissue, the adapter plate is fixedly installed in the electrode shell 8, and the electrode support platform 800 at the front end of the electrode shell 8 can support the rear end of the electrode body 1. For example, the electrode support platform 800 can support the connecting portion 102 at the rear end of the electrode body 1.

[0102] In a specific embodiment, Figures 9 to 11 As shown, the electrode housing 8 includes a first fixed housing 80 and a second fixed housing 81;

[0103] The first fixed housing 80 is provided with limited side walls 801 on both sides, the adapter circuit board 60 is arranged on the first fixed housing 80 and is located between the limited side walls 801 on both sides, and the electrode support platform 800 is arranged on the first fixed housing 80, and the height of the electrode support platform 800 is the same as the thickness of the adapter circuit board 60;

[0104] The second fixed housing 81 is detachably fixed to the first fixed housing 80 . A pressing beam 812 is provided on the inner side of the second fixed housing 81 . The pressing beam 812 is pressed against the adapter circuit board 60 .

[0105] In this embodiment, the electrode housing 8 includes a first fixed housing 80 as a lower housing and a second fixed housing 81 as an upper housing. After the limiting side walls 801 are set on both sides of the first housing, a through groove is formed at the upper end of the first housing, and an installation space is formed between the limiting side walls 801 on both sides. The adapter circuit board 60 can be installed in the installation space, and the adapter circuit board 60 is limited by the limiting side walls 801 on both sides. At the same time, after the through groove is formed in the first housing, the opening at the rear end is also convenient for connecting the adapter plug board 61 with the external detection equipment, and the opening at the front end can facilitate the installation of the rear end of the electrode body 1. The electrode support platform 800 is a boss formed at the front end of the first housing. The height of the electrode support platform 800 is the same as the thickness of the adapter circuit board 60, so that the rear end of the electrode body 1 can be supported by the electrode support platform 800 and can be kept on a level close to or the same as the adapter circuit board 60, so that the electrode body 1 and the electrode housing 8 can be kept parallel to each other, ensuring the accuracy of the surgical implantation position.

[0106] The first fixed housing 80 and the second fixed housing 81 can be connected by upper and lower buckles 810. Specifically, Fig.10 As shown, side walls extending downward can be provided on both sides of the second fixed housing 81, and the lower ends of the side walls protrude horizontally to form buckles 810. When installed, the second fixed housing 81 is installed on the first fixed housing 80 from top to bottom, the side walls of the second fixed housing 81 are located outside the limiting side walls 801 of the first fixed housing 80, and the buckle 810 at the lower end of the second fixed housing 81 is snapped onto the lower end surface of the first fixed housing 80.

[0107] Specifically, in this embodiment, the electrode support platform 800 is used to support the connecting portion 102 at the rear end of the electrode body 1 , and the extended portion 101 at the rear end of the electrode body 1 corresponds to the wiring pad 62 in the upper and lower directions.

[0108] Further, such as Fig. 9 As shown, a tube fixing structure 811 is provided at the upper end of the second fixed housing 81;

[0109] The neural electrode also includes a rubber hose 92, a connecting capillary 91 and a connecting tube 90. The connecting capillary 91 is an L-shaped tube. The rubber hose 92 is detachably fixedly connected to the tube fixing structure 811. The first end of the connecting capillary 91 is fixedly connected to the rubber hose 92. The second end of the connecting capillary 91 is fixedly connected to the connecting tube 90. The lower end of the connecting tube 90 is sleeved and fixed on the connecting column 4.

[0110] Specifically, in this embodiment, the lower end of the connecting tube 91 can be sleeved and fixed with the connecting tube 90, and the two can be sealed by interference fit. The connecting tube 91 adopts an L-shaped tube, so that the upper part of the connecting tube 91 is a horizontal tube after bending, which can be kept in the same horizontal direction with the adapter circuit board 60 and the adapter socket after installation, so as to facilitate the connection of various devices. The upper end of the connecting tube 91 is connected to the hose 92, and the hose 92 is horizontally fixedly connected to the tube fixing structure 811. Specifically, the hose 92 can be plugged into the tube fixing structure 811 and fixed by the corresponding buckle 810.

[0111] In one embodiment, the hose 92 is a medical silicone hose 92, and the connecting tube 91 can be an L-shaped metal tube. To facilitate installation and removal of the hose 92, a through installation groove can be provided on the tube fixing structure 811, and the installation groove is an arc groove, and the hose 92 can be clamped and fixed in the installation groove.

[0112] In order to better fix the adapter circuit board 60, as Figure 8 and Fig.10 As shown, in this embodiment, a positioning column 802 is provided on the first fixed housing 80, and a positioning hole 600 is provided on the adapter circuit board 60, and the positioning hole 600 is plugged and matched with the positioning column 802. The positioning column 802 can be set to multiple, and similarly, the positioning hole 600 can also be set to a corresponding multiple.

[0113] According to another aspect of the present invention, a method for preparing a neural electrode is provided, which is used to prepare the above-mentioned neural electrode. The method for preparing a neural electrode comprises the following steps:

[0114] preparing an electrode layer;

[0115] A microchannel 2 is formed on the surface of the electrode layer by 3D printing;

[0116] The electrode layer is processed to obtain an electrode body 1 that meets the designed shape.

[0117] In this embodiment, the microchannel 2 is formed by 3D printing to achieve customized preparation of the neural electrode. The processing of the electrode layer includes processing the prepared electrode layer by cutting and etching to obtain an electrode body 1 that meets the designed shape.

[0118] In one embodiment, to improve the preparation accuracy of the electrode layer, preparing the electrode layer includes:

[0119] Depositing a sacrificial layer on the substrate: Specifically, a 10-nanometer titanium and a 500-nanometer aluminum layer can be sequentially deposited on the silicon wafer substrate by magnetron sputtering as sacrificial layers for release.

[0120] A biocompatible material is used to form a bottom layer on the sacrificial layer. Specifically, a layer of polyimide with a thickness of 4 to 6 microns can be prepared by spin coating on the sacrificial layer as the bottom layer.

[0121] The bottom layer is patterned by photolithography. Specifically, a photoresist is spin-coated on the bottom layer, and then photolithography and development processes are performed in sequence to process the photoresist in the same shape as the designed substrate 10, and the pattern is transferred to the bottom layer by reactive ion etching. At this time, the shape of the bottom layer is the same as the shape of the substrate 10 in the designed neural electrode, and the bottom layer is equivalent to the substrate 10 in the neural electrode structure.

[0122] A photolithography process and a metal deposition process are used to form metal wiring 11 on the bottom layer. Specifically, acetone is used to remove the photoresist remaining after etching, and the photoresist is spin-coated again, and then photolithography and development processes are performed in sequence to process the photoresist of the same shape as the designed metal wiring 11. A magnetron sputtering deposition method is used to deposit metal, and after the deposition is completed, acetone is used to dissolve and peel the photoresist to obtain a conductive pattern on the bottom layer, which is the metal wiring 11. It can be understood that when the metal wiring 11 includes multiple metal layers in the above-mentioned embodiment, 10 nanometers of titanium, 50 nanometers of platinum, and 50 nanometers of gold need to be deposited in sequence during magnetron sputtering deposition to form a first metal layer 110, a second metal layer 111, and a third metal layer 112, respectively.

[0123] An insulating intermediate layer is formed on the bottom layer using a biocompatible material, and the rear end of the metal wiring 11 is exposed on the bottom layer to form a lead pad 5. Specifically, chemical vapor deposition polyparaxylene can be used to make the intermediate layer, and the intermediate layer is not patterned at this time. In other words, the shape of the intermediate layer is not the same as the shape of the insulating layer 13 designed in the electrode body 1, but its function and position are the same as those of the insulating layer 13. In subsequent processing, the intermediate layer can be processed by cutting to obtain an insulating layer 13 that meets the designed shape.

[0124] When the structure of the electrode body 1 further includes a support layer 14, the method for preparing the electrode layer in this embodiment further includes:

[0125] A support layer 14 with support performance is formed on the intermediate layer by using a photolithography process and a deposition process, and the support layer 14 is patterned. Specifically, before the intermediate layer is cut or processed, a magnetron sputtering deposition method can be used to sequentially deposit 10 nanometers of titanium and 50 nanometers of copper on the intermediate layer as electroplating seed layers; spin-coat the photoresist again, and then sequentially perform photolithography and development processes to process the photoresist of the same shape as the designed nickel support layer 14; and by a direct current electroplating method, electro-deposit about 15 microns of nickel, and then selectively etch away the titanium and copper seed layers to obtain a patterned support layer 14. The shape of the support layer 14 obtained at this time is consistent with the shape of the designed support layer 14.

[0126] When the neural electrode further includes a reinforcement beam 3 and a connection column 4, the microchannel 2, the reinforcement beam 3 and the connection column 4 can be integrally manufactured on the surface of the support layer 14 by a high-precision photopolymerization 3D printing method.

[0127] When the microchannel 2, the reinforcement beam 3, the connecting column 4 and the support layer 14 need to be covered with a protective layer, in this embodiment, the electrode layer is processed to obtain an electrode body 1 that meets the design shape, including:

[0128] A deposition process is used to form a protective layer on the microchannel 2 and the support layer 14. Specifically, chemical vapor deposition polyparaxylene can be used to cover the exposed microchannel 2, reinforcement beam 3, connection column 4 and support layer 14. At this time, the protective layer and the insulating layer 13 are both unpatterned layer structures, so it is also necessary to cut the protective layer and the intermediate layer according to the designed shape to define the overall shape of the electrode body 1.

[0129] The bottom layer is separated from the sacrificial layer. Specifically, the electrode body 1 can be released from the silicon wafer by using an electrolytic aluminum method.

[0130] An electrical detection point 12 is formed on the first side of the electrode body 1. Specifically, the electrical detection point 12 can be formed by processing the bottom layer of the electrode body 1 and the first metal layer 110 (when the first metal layer 110 is included) by etching at a designed position.

[0131] Furthermore, the method further comprises the following steps:

[0132] The adapter 6 is electrically connected to the lead pad 5. Specifically, the specific connection method between the adapter 6 and the lead pad 5 is designed according to its specific structure. In one embodiment, when the adapter 6 includes a structure as in the above embodiment, the wiring pad 62 in the adapter 6 and the lead pad 5 are electrically interconnected in the vertical direction through the anisotropic conductive film 7 under the action of heat and pressure.

[0133] The adapter 6 is installed in the electrode housing 8, and the flow channel inlet of the microchannel 2 is connected to the tube assembly 9. Specifically, the adapter 6 can be installed on the first fixed housing 80 first, and then the rubber hose 92, the connecting tube 91 and the connecting tube 90 in the tube assembly 9 are installed in sequence, and then the second fixed housing 81 is fastened and fixed on the first fixed housing 80, and finally the rubber hose 92 in the tube assembly 9 is fixed in the installation groove of the second fixed housing 81.

[0134] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Within the spirit and principle of the present invention, any modification, equivalent replacement, improvement, etc. made shall be included in the protection scope of the present invention.

Claims

1. A neural electrode with drug delivery capability, characterized in that: include: An electrode body, wherein the intervention end of the electrode body is provided with a plurality of electrical detection points, the electrical detection points are located on a first side of the electrode body, and the connection end of the electrode body is provided with a lead-out pad; The microfluidic channel is arranged on the second side of the electrode body, the front end of the microfluidic channel extends to the intervention end of the electrode body and can intervene in the tissue along the intervention end, the front end of the microfluidic channel is provided with a channel outlet, and the rear end of the microfluidic channel is provided with a channel inlet.

2. The neural electrode with drug delivery capability according to claim 1, characterized in that: The electrode body comprises a substrate, a metal wiring, an insulating layer and a supporting layer, wherein the substrate and the insulating layer are made of biocompatible materials, the metal wiring is arranged on the substrate, the insulating layer covers the metal wiring, and the supporting layer covers the insulating layer; A plurality of electrical detection points are arranged on the substrate, and a partial area of ​​the metal wiring is exposed through the electrical detection points, and a rear end of the metal wiring is exposed on the substrate to form the lead pad; The microchannel is arranged on the supporting layer.

3. The neural electrode with drug delivery capability according to claim 2, characterized in that: The metal wiring includes a first metal layer, a second metal layer and a third metal layer stacked in sequence on the substrate, the area on the first metal layer corresponding to the detection hole and the lead-out pad is selectively removed, and a partial area of ​​the second metal layer is exposed through the electrical detection point; the first metal layer is titanium, the second metal layer is platinum, and the third metal layer is gold.

4. The neural electrode with drug delivery capability according to claim 2, characterized in that: The material of the support layer is nickel.

5. The neural electrode with drug delivery capability according to claim 2, characterized in that: The rear end of the substrate includes a connecting portion and an extension portion connected in sequence, the rear end of the metal wiring extends to the extension portion after passing through the connecting portion, and the lead pad includes the extension portion and the metal wiring located on the extension portion; The rear end of the insulating layer covers the metal wiring located at the connecting portion, and the rear end of the supporting layer covers the insulating layer corresponding to the connecting portion.

6. The neural electrode with drug delivery capability according to claim 5, characterized in that: The neural electrode further comprises a reinforcing beam and a connecting tube. The reinforcing beam is arranged at a position corresponding to the supporting layer and the connecting portion. The connecting tube is arranged on the reinforcing beam. The rear end of the microchannel passes through and is connected with the lower end of the connecting tube.

7. The neural electrode with drug delivery capability according to claim 6, characterized in that: The support layer, the reinforcement beam, the connecting pipe and the microchannel are conformally coated with a protective layer, and the protective layer is made of a biocompatible material.

8. The neural electrode with drug delivery capability according to claim 1, characterized in that: The neural electrode further includes an adapter, which is electrically connected to the lead-out pad and is used to be electrically connected to a detection device.

9. The neural electrode with drug delivery capability according to claim 8, characterized in that: The adapter includes an adapter circuit board, an adapter plug board and a cable pad. The adapter plug board and the cable pad are electrically connected to the first end and the second end of the adapter circuit board respectively. Multiple interfaces are set at both ends of the adapter plug board, and the cable pad is electrically connected to the lead-out pad.

10. The neural electrode with drug delivery capability according to claim 9, characterized in that: The lead pad and the wiring pad are arranged vertically opposite to each other and are electrically connected to each other through an anisotropic conductive film, so that the metal wiring on the lead pad is electrically interconnected with the wiring pad in a vertical direction.

11. The neural electrode with drug delivery capability according to claim 9, characterized in that: The neural electrode further comprises an electrode shell, the adapter is fixedly arranged in the electrode shell, an electrode support platform is arranged on the electrode shell, and the electrode support platform plays a supporting role for the rear end of the electrode body.

12. The neural electrode with drug delivery capability according to claim 11, characterized in that: The electrode shell includes a first fixed shell and a second fixed shell; The first fixed housing is provided with limited side walls on both sides, the adapter circuit board is arranged on the first fixed housing and is located between the limited side walls on both sides, the electrode support platform is arranged on the first fixed housing, and the height of the electrode support platform is the same as the thickness of the adapter circuit board; The second fixed shell is detachably fixed to the first fixed shell, and a pressing beam is arranged on the inner side of the second fixed shell, and the pressing beam is pressed on the adapter circuit board.

13. The neural electrode with drug delivery capability according to claim 12, characterized in that: The upper end of the second fixed shell is provided with a tube fixing structure; The neural electrode also includes a rubber tube, a connecting thin tube and a connecting column, wherein the connecting thin tube is an L-shaped tube; the rubber tube is detachably fixedly connected to the tube fixing structure, the first end of the connecting thin tube is fixedly connected to the rubber tube, the second end of the connecting thin tube is fixedly connected to the connecting column, and the lower end of the connecting column is sleeved and fixed on the connecting tube.

14. The neural electrode with drug delivery capability according to claim 12, characterized in that: The first fixed shell is provided with a positioning column, and the adapter circuit board is provided with a positioning hole, and the positioning hole is plugged and matched with the positioning column.

15. A method for preparing a neural electrode, characterized in that: Used to prepare the neural electrode according to any one of claims 1 to 14, the neural electrode preparation method comprises the following steps: preparing an electrode layer; The microchannel is formed on the surface of the electrode layer by 3D printing; The electrode layer is processed to obtain the electrode body conforming to the designed shape.

16. The method for preparing a neural electrode according to claim 15, characterized in that: The preparation of the electrode layer comprises: depositing a sacrificial layer on the substrate; forming a bottom layer on the sacrificial layer using a biocompatible material; The bottom layer is patterned using a photolithography process; Using photolithography and metal deposition processes to form metal wiring on the bottom layer; An insulating intermediate layer is formed on the bottom layer using a biocompatible material, and the rear end of the metal wiring is exposed on the bottom layer to form a lead pad.

17. The method for preparing a neural electrode according to claim 16, characterized in that: The preparation of the electrode layer further comprises: A supporting layer with supporting properties is formed on the intermediate layer by adopting a photolithography process and a deposition process, and the supporting layer is patterned.

18. The method for preparing a neural electrode according to claim 17, characterized in that: The electrode layer is processed to obtain the electrode body conforming to the designed shape, comprising: A deposition process is used to form a protective layer on the microfluidic channel and the support layer; Cut the protective layer and the middle layer according to the designed shape; separating the bottom layer from the sacrificial layer; An electrical detection point is formed on the first side of the electrode body.

19. The method for preparing a neural electrode according to claim 15, characterized in that: The following steps are also included: Electrically connect the adapter to the lead pad; Install the adapter into the electrode housing and connect the flow channel inlet of the microfluidic channel to the tube assembly; Secure the tube assembly to the electrode housing.

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