Neural electrode with drug delivery capability and method of making same

Abstract

The application discloses a nerve electrode with drug delivery capability and a preparation method thereof, and relates to the technical field of nerve electrodes, and comprises the following parts: an electrode main body, a plurality of electrical detection points are arranged on the intervention end of the electrode main body, the electrical detection points are located on the first side of the electrode main body, and the connecting end of the electrode main body is provided with a lead-out pad; a micro flow channel is arranged on the second side of the electrode main body, the front end of the micro flow channel extends to the intervention end of the electrode main body and can enter the tissue along with the intervention end, the front end of the micro flow channel is provided with a flow channel outlet, and the rear end of the micro flow channel is provided with a flow channel inlet. The application realizes the technical effect that drug delivery to the implanted electrode area is more convenient, and since the injection equipment for drug delivery only needs to be connected with the flow channel inlet and does not need to enter the tissue, the damage to the tissue is reduced, and even if the drug needs to be frequently delivered, the damage to the tissue can be better reduced.

Description

TECHNICAL FIELD

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

[0002] In the research of neuroscience, the electrode is one of the most core research means, which can directly reflect the state and functional connection of the nerve by recording the electrical activity of the nervous system. At the same time, in many experiments, drug delivery to the central nervous system as a whole or to specific areas is needed to assist the research of nerve function or to verify the function of the drug.

[0003] Due to the existence of the blood-brain barrier, the drug blocking phenomenon makes it difficult to achieve drug delivery to the central nervous system by oral or intravenous injection, and it is even more difficult to achieve delivery to specific areas. Therefore, the method commonly used in experiments at present is to use a micro-injection device combined with a stereotaxic instrument, and after positioning, the syringe is inserted and micro-injection is performed.

[0004] However, in the whole experimental process, the drug injection operation in the electrode implantation area is difficult, and the micro-injection often needs to be performed multiple times, which frequently uses the syringe to cause great harm to the experimental animals and may affect the experimental results. SUMMARY

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

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

[0007] An electrode body, the intervention end of the electrode body is provided with a plurality of electrical detection points, 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-out pad;

[0008] A micro-channel is arranged on the second side of the electrode body, the front end of the micro-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 micro-channel is provided with a channel outlet, and the rear end of the micro-channel is provided with a channel inlet.

[0009] Further, the neural electrode further comprises an adapter, the connection end of the electrode body is provided with a lead-out pad, the adapter is electrically connected with the lead-out pad, and the adapter is used for electrically connecting with a detection device.

[0010] Further, the electrode body comprises a substrate, a metal wiring, an insulation layer and a support layer, the substrate and the insulation layer are made of biocompatible material, the metal wiring is arranged on the substrate, the insulation layer covers the metal wiring, and the support layer covers the insulation layer.

[0011] A plurality of electrical detection points are arranged on the substrate, part of the metal wiring is exposed through the electrical detection points, and the rear end of the metal wiring is exposed on the substrate and forms the lead-out pad.

[0012] The micro flow channel is arranged on the support layer.

[0013] Further, the metal wiring comprises a first metal layer, a second metal layer and a third metal layer arranged on the substrate in sequence, the area corresponding to the electrical detection point and the lead-out pad on the first metal layer is selectively removed, and part 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] Further, the material of the support layer is nickel.

[0015] Further, the rear end of the substrate comprises a connecting part and an extension part connected in sequence, the rear end of the metal wiring extends to the extension part through the connecting part, and the lead-out pad comprises the extension part and the metal wiring on the extension part.

[0016] The rear end of the insulation layer covers the metal wiring in the connecting part, and the rear end of the support layer covers the insulation layer corresponding to the connecting part.

[0017] Further, the neural electrode further comprises a reinforcing beam and a connecting column, the reinforcing beam is arranged at a position corresponding to the connecting part of the support layer, the connecting column is arranged on the reinforcing beam, and the rear end of the micro flow channel passes through and communicates with the lower end of the connecting column.

[0018] Further, the support layer, the reinforcing beam, the connecting column and the micro flow channel are conformally coated with a protective layer made of biocompatible material.

[0019] Further, the adapter comprises an adapter circuit board, an adapter plugboard and a flat cable pad, the adapter plugboard and the flat cable pad are electrically connected to the first end and the second end of the adapter circuit board respectively, the two ends of the adapter plugboard are provided with a plurality of interfaces, and the flat cable pad is electrically connected with the lead-out pad.

[0020] Further, the lead-out pad is arranged opposite to the flat cable pad in the vertical direction, and the lead-out pad and the flat cable pad are electrically connected by an anisotropic conductive film, so that the metal wiring on the lead-out pad and the flat cable pad are electrically connected in the vertical direction.

[0021] Further, the neural electrode further comprises an electrode shell, the adapter plate is fixed in the electrode shell, and an electrode support table is arranged on the electrode shell to support the rear end of the electrode body.

[0022] Further, the electrode shell comprises a first fixed shell and a second fixed shell.

[0023] The first fixed shell is provided with limiting side walls on both sides, the adapter circuit board is arranged on the first fixed shell and located between the limiting side walls on both sides, and the electrode support table is arranged on the first fixed shell and has the same height as the thickness of the adapter circuit board.

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

[0025] Further, the upper end of the second fixed shell is provided with a tube fixing structure.

[0026] The neural electrode further comprises a rubber tube, a connecting tube and a connecting pipe, the connecting tube is an L-shaped tube, the rubber tube is detachably fixedly connected with the tube fixing structure, the first end of the connecting tube is fixedly connected with the rubber tube, the second end of the connecting tube is fixedly connected with the connecting pipe, and the lower end of the connecting pipe is fixedly sleeved on the connecting column.

[0027] Further, the first fixed shell is provided with a positioning column, and the adapter circuit board is provided with a positioning hole which is insertedly matched with the positioning column.

[0028] According to another aspect of the present application, a neural electrode preparation method is provided for preparing the neural electrode, and the neural electrode preparation method comprises the following steps:

[0029] Preparation of an electrode layer;

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

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

[0032] Further, the preparation of the electrode layer comprises:

[0033] Depositing a sacrificial layer on a substrate;

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

[0035] performing patterning on the bottom layer using a photolithography process;

[0036] forming metal wires on the bottom layer using a photolithography process and a metal deposition process;

[0037] forming an insulating intermediate layer on the bottom layer using a biocompatible material, and exposing back ends of the metal wires on the bottom layer to form lead-out pads.

[0038] Further, the preparation of the electrode layer further comprises:

[0039] forming a support layer with support performance on the intermediate layer using a photolithography process and a deposition process, and performing patterning on the support layer.

[0040] Further, processing the electrode layer to obtain the electrode body in a designed shape comprises:

[0041] forming a protective layer on the micro flow channel and the support layer using a deposition process;

[0042] cutting the protective layer and the intermediate layer according to the designed shape;

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

[0044] forming an electrical detection point on a first side of the electrode body.

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

[0046] electrically connecting the adapter to the lead-out pads;

[0047] mounting the adapter into the electrode shell, and making the flow channel inlet of the micro flow channel communicate with the tube assembly;

[0048] fixing the tube assembly on the electrode shell.

[0049] The electrode main body is provided with a plurality of electrical detection points at the insertion end, the electrical detection points are located at the first side of the electrode main body, and the connecting end of the electrode main body is provided with a lead-out pad; a micro flow channel is arranged at the second side of the electrode main body, the front end of the micro flow channel extends to the insertion end of the electrode main body and can be inserted into the tissue along with the insertion end, the front end of the micro flow channel is provided with a flow channel outlet, and the rear end of the micro flow channel is provided with a flow channel inlet; and an adapter is electrically connected with the lead-out pad and used for electrical connection with a detection device. In the application, the front end of the micro flow channel can be inserted into the tissue along with the insertion end of the electrode main body, and the rear end of the micro flow channel is close to the rear end of the electrode main body. After the neural electrode is implanted into the tissue, the flow channel outlet of the micro flow channel remains in the tissue, and the flow channel inlet remains outside the tissue. The micro flow channel can be used for drug delivery to the tissue, so that the drug delivery to the implanted electrode area is more convenient, the injection equipment for drug delivery only needs to be connected with the flow channel inlet and does not need to be inserted into the tissue, the damage to the tissue is reduced, even if the drug needs to be frequently delivered, the damage to the tissue can be better reduced, and the problems that it is difficult to perform the drug injection surgery in the implanted electrode area and the experimental animal is damaged by frequent use of the syringe in the prior art are solved. BRIEF DESCRIPTION OF DRAWINGS

[0050] The drawings constituting a part of the present application are used to provide a further understanding of the present application, so that other features, objects and advantages of the present application become more apparent. The schematic embodiment drawings of the present application and the description thereof are used to explain the present application, and do not constitute an improper limitation on the present application. In the drawings:

[0051] Figure 1 is a structure schematic view of the micro flow channel combined with the electrode main body according to the embodiment of the present application;

[0052] Figure 2 is a side structure schematic view of Figure 1 ;

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

[0054] Figure 4 is a side structure schematic view of the electrode main body according to the embodiment of the present application;

[0055] Figure 5 is a tip enlarged structure schematic view of the electrode main body according to the embodiment of the present application;

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

[0057] Figure 7is a structural schematic diagram of the adapter according to an embodiment of the present application;

[0058] Figure 8 is a schematic diagram of the connection between the flat cable pad and the lead pad of the electrode body of the adapter according to an embodiment of the present application;

[0059] Figure 9 is a structural schematic diagram of the electrode shell according to an embodiment of the present application;

[0060] Figure 10 is Figure 9 an exploded structural schematic diagram;

[0061] Figure 11 is a structural schematic diagram of the second fixing shell according to an embodiment of the present application;

[0062] In the drawings: 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, insulating layer; 14, support layer; 2, micro flow channel; 20, flow channel outlet; 3, reinforcing beam; 4, connecting column; 5, lead pad; 6, adapter; 60, adapter circuit board; 600, positioning hole; 61, adapter plugboard; 610, interface; 62, flat cable pad; 7, anisotropic conductive film; 8, electrode shell; 80, first fixing shell; 800, electrode support table; 801, limiting side wall; 802, positioning column; 810, buckle; 811, tube fixing structure; 812, pressing beam; 81, second fixing shell; 9, tube assembly; 90, connecting tube; 91, connecting thin tube; 92, rubber tube. DETAILED DESCRIPTION

[0063] In order for those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor should fall within the scope of protection of the present application.

[0064] It should be noted that the terms "first", "second", and the like in the specification and claims of the present application and the above-described drawings are used to distinguish similar objects, and do not necessarily have to describe a specific order or sequence. It should be understood that the data thus used can be interchanged under appropriate circumstances, so as to describe the embodiments of the present application described herein.

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

[0066] In addition, in addition to indicating the orientation or positional relationship, the above-mentioned partial terms can also be used to indicate other meanings, for example, the term "upper" can also be used to indicate a certain dependent relationship or connection relationship in some cases. For those skilled in the art, the specific meaning of these terms in the present application can be understood according to the specific circumstances.

[0067] In addition, the terms "provided", "provided with", "connected", "fixed", etc. should be broadly understood. For example, "connected" can be fixedly connected, detachably connected, or integrally constructed; it can be mechanically connected or electrically connected; it can be directly connected or indirectly connected through an intermediate medium, or it can be internal communication between two devices, elements or components. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0068] In addition, the meaning of the term "a plurality of" should be two and more than two.

[0069] It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict. The present application will be described in detail below with reference to the drawings and in combination with the embodiments.

[0070] To solve the related technical problems, as shown in Figures 1 to 4 The present application provides a neural electrode with drug delivery capability, comprising:

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

[0072] A micro-channel 2 is arranged at the second side of the electrode body 1, the front end of the micro-channel 2 extends to the intervention end of the electrode body 1 and can be inserted into the tissue with the intervention end, the front end of the micro-channel 2 is provided with a channel outlet 20, and the rear end of the micro-channel 2 is provided with a channel inlet.

[0073] In the embodiment, the insertion end of the electrode body 1 is in an elongated structure, which can be inserted into the tissue, such as the brain tissue of an animal. The rear end of the electrode body 1 is outside the tissue and needs to be electrically connected to the detection device to transmit the electrical signal to the detection device, so the rear end of the electrode body 1 can be in a wider structure to facilitate the connection with the detection device. In the embodiment, the insertion 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 insertion end is inserted into the tissue, the electrical detection points 12 at different positions can detect the signals at different positions in the tissue. The rear end of the electrode body 1 is a connection end, and the connection end is provided with a lead-out pad 5. The metal part in the electrode body 1 for transmitting the signal is exposed on the lead-out pad 5, so as to facilitate the transmission of the signal to the outside.

[0074] On this basis, in the embodiment, the electrode body 1 is provided with a micro flow channel 2. The micro flow channel 2 is in an elongated flow channel structure, which can enter the tissue along with the insertion end of the electrode body 1. In order to avoid interference between the micro flow channel 2 and the electrical detection points 12, the micro flow 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 opposite sides of the electrode body 1, which can provide sufficient arrangement space, especially for the electrode body 1 with a flat insertion end. The front end opening of the micro flow channel 2 forms a flow channel outlet 20, and the rear end opening of the micro flow channel 2 forms a flow channel inlet. After the electrode body 1 is inserted into the tissue, the flow channel outlet 20 is located in the tissue, and the flow channel inlet is located outside the tissue. The injection device can be connected to the flow channel inlet to inject the medicament into the micro flow channel 2 through the flow channel inlet, and the medicament flows out through the flow channel outlet 20 and enters the vicinity of the electrode implantation area.

[0075] In the embodiment, the front end of the micro flow channel 2 can enter the tissue along with the insertion end of the electrode body 1, and the rear end of the micro flow channel 2 is close to the rear end of the electrode body 1. After the neural electrode is implanted into the tissue, the flow channel outlet 20 of the micro flow channel 2 remains inside the tissue, and the flow channel inlet remains outside the tissue. The micro flow channel 2 can deliver the drug to the tissue, so that the drug delivery to the implanted electrode area is more convenient. Since the injection device for drug delivery only needs to be connected to the flow channel inlet and does not need to be inserted into the tissue, the damage to the tissue is reduced. Even if the drug needs to be delivered frequently, the damage to the tissue can be better reduced, thereby solving the problems in the related art that it is difficult to perform the drug injection surgery in the implanted electrode area, and the frequent use of the syringe causes great harm to the experimental animal.

[0076] In one embodiment, the micro flow channel 2 is a hollow tubular structure with an inner diameter of less than 100 microns. In order to reduce the resistance in the implantation process, the flow channel outlet 20 at the front end of the micro flow channel 2 can be a 45° beveled cross section.

[0077] In one embodiment of the electrode body 1, as shown in Figures 3 to 6 the electrode body 1 comprises a substrate 10, a metal wiring 11, an insulating layer 13 and a support layer 14, the substrate 10 and the insulating layer 13 are made of a biocompatible material, the metal wiring 11 is arranged on the substrate 10, the insulating layer 13 covers the metal wiring 11, and the support layer 14 covers the insulating layer 13;

[0078] The substrate 10 is provided with a plurality of electrical detection points 12, and the metal wiring 11 is exposed at the electrical detection points 12, and the rear end of the metal wiring 11 is exposed on the substrate 10 and forms a lead-out pad 5.

[0079] The micro-channel 2 is arranged on the support layer 14.

[0080] Specifically, to solve the problem of poor biocompatibility of the neural electrode in the related art, which can easily cause biological immune response in the long-term implantation process, the substrate 10 and the insulating layer 13 of the electrode body 1 in the embodiment are made of a biocompatible material. 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 the material has good adhesion with the metal wiring. The part of the substrate 10 corresponding to the intervention end can be etched to form the electrical detection point 12, and the rear end of the substrate 10 can be etched to form the shape of the lead-out pad 5, and the metal wiring 11 at these positions will be exposed to realize the reception and transmission of the neural electrical physiological signal.

[0081] The metal wiring 11 is the second layer of the entire electrode body 1, and the metal wiring 11 is arranged on the substrate 10, and the overall thickness can be about 100 nanometers, which plays a role of one-to-one corresponding connection of the electrical detection point 2 and the lead-out pad 54 of each channel of the electrode. The metal wiring 11 can be prepared by photolithography process and deposition process, so as to form a plurality of signal channels with high precision, and different signal channels correspond to different electrical detection points 12.

[0082] In one embodiment, as shown in Figure 6 the metal wiring 11 comprises a first metal layer 110, a second metal layer 111 and a third metal layer 112 arranged on the substrate 10 in sequence, the regions of the first metal layer 110 corresponding to the electrical detection points 12 and the lead-out pad 5 are selectively removed, and the second metal layer 111 is exposed at the electrical detection points 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 embodiment, the metal used by the metal wiring 11 is a three-layer structure, 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 of the second metal layer 111. At the position where the electrical detection site and the lead-out pad 5 expose the metal wiring 11, the first metal layer 110 will be selectively removed to achieve that the second metal layer 111 becomes the metal actually in contact with the neural tissue. The reason is that the second metal layer 111 adopts platinum material, and the interface of platinum has lower electrochemical impedance, which can have higher signal-to-noise ratio when collecting electrophysiological signals. The third metal layer 112 made of gold material at the top layer plays a role in reducing the resistance of the metal wiring 11 itself, and its good ductility can still enable the metal wiring 11 to be electrically conductive in the case of a certain bending.

[0084] In an embodiment, the total 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, and the insulating layer 13 can adopt polyimide or parylene material, and preferably adopts parylene. The insulating layer 13 completely covers the metal wiring 11 to avoid the metal wiring 11 being short-circuited by contacting with the body fluid. Parylene is a material with good biological safety, which is safe and reliable. In an embodiment, the thickness of the insulating layer 13 can be about 2 micrometers.

[0086] The support layer 14 is the fourth layer of the entire electrode body 1, and the support layer 14 is made of a material with support performance, such as nickel. The support layer 14 increases the rigidity of the insertion end portion of the electrode body 1 to better insert into the tissue, and the support layer 14 also has good toughness after adopting nickel, and will not be broken under a large bending angle, greatly reducing the risk of electrode breakage during the operation. In an embodiment, the thickness of the support layer 14 is about 15 to 20 micrometers.

[0087] It should be noted that the front end portion of the electrode body 1 needs to be inserted into the tissue, and therefore is designed to be an elongated structure, while the rear end portion needs to be connected to the adapter 6, and therefore is designed to be a wider structure. Therefore, in order to increase the strength of the abrupt change between the front end portion and the rear end portion, as shown in FIGS. 1 and 2, the rear end of the substrate 10 in the embodiment includes a connection portion 102 and an extension portion 101 connected in sequence, and the rear end of the metal wiring 11 extends to the extension portion 101 through the connection portion 102, and the lead-out pad 5 includes the extension portion 101 and the metal wiring 11 on the extension portion 101. Figure 1 Figure 3 ​​

[0088] The rear end of the insulating layer 13 covers the metal wiring 11 at the joint 102, and the rear end of the support layer 14 covers the insulating layer 13 corresponding to the joint 102.

[0089] Specifically, the joint 102 in the embodiment is a wider extension 101 and a narrower front end part of the joint electrode body 1, and the width of the joint 102 is tapered. In an embodiment, the joint 102 is triangular, and the provision of the joint 102 can increase the strength of the transition between the front end part and the rear end part, and avoid deformation or breakage of the front end part of the electrode body 1. The wider extension 101 can be square, and the extension 101 mainly includes the substrate 10 and the metal wiring 11 on the substrate 10, and the substrate 10 and the metal wiring 11 of this part naturally form the lead bonding pad 5 of the electrode body. Therefore, the rear end of the insulating layer 13 only covers the metal wiring 11 of the joint 102, and the rear end of the support layer 14 also only covers the insulating layer 13 corresponding to the joint 102. In other words, the electrode body 1 still needs to maintain the insulation performance and certain support performance in the area corresponding to the joint 102, and only exposes the metal wiring 11 at the position corresponding to the extension 101 for electrical connection with the adapter 6.

[0090] In an embodiment, as shown in Figure 1 and Figure 2 The neural electrode further includes a reinforcing beam 3 and a connecting column 4, the reinforcing beam 3 is arranged at the position corresponding to the joint 102 of the support layer 14, and the connecting column 4 is arranged on the reinforcing beam 3, and the rear end of the micro flow channel 2 passes through and communicates with the lower end of the connecting column 4.

[0091] Specifically, in the embodiment, since the micro flow channel 2 is also an elongated structure, in order to facilitate the injection of the medicament into the micro flow channel 2, a connecting column 4 with a larger diameter needs to be arranged at the rear end of the micro flow channel 2. After the connecting column 4 is arranged, there is a diameter transition at the connecting position of the connecting column 4 and the micro flow channel 2, which reduces the structural strength. Therefore, in the embodiment, a reinforcing beam 3 is first arranged at the position corresponding to the joint 102 of the support layer 14, the rear end of the micro flow channel 2 extends into the reinforcing beam 3, and the lower end of the connecting column 4 communicates with the flow channel inlet of the micro flow channel 2. The provision of the reinforcing beam 3 can increase the strength of the size transition of the micro flow channel 2 to the connecting column 4, and can improve the yield during preparation and provide stable drug delivery capability.

[0092] In an embodiment, the connecting column 4 is a hollow cylinder with a height of 2 millimeters and an outer diameter of 1 millimeter. The connecting column 4 can be perpendicular to the surface of the support layer 14.

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

[0094] To facilitate the connection of the neural electrode with the detection equipment, as shown in Figure 7 and Figure 8 , the neural electrode further comprises an adapter 6, which is electrically connected with the lead-out pad 5 and is also used for electrical connection with the detection equipment.

[0095] In one embodiment of the adapter 6, the adapter 6 comprises an adapter circuit board 60, an adapter plugboard 61 and a flat cable pad 62, the adapter plugboard 61 and the flat cable pad 62 are respectively electrically connected at the first end and the second end of the adapter circuit board 60, and the two ends of the adapter plugboard 61 are provided with a plurality of interfaces 610, and the flat cable pad 62 is electrically connected with the lead-out pad 5.

[0096] Specifically, in this embodiment, the two ends of the adapter plugboard 61 have a plurality of interfaces 610, which can all be Omnetics interfaces 610. The adapter plugboard 61 can be welded and fixed with the adapter circuit board 60, and the Omnetics interface 610 is a common interface 610 for many current neural electrophysiological signal detection equipment, so the adapter plugboard 61 can be compatible with various equipment, and a single interface 610 can support up to 16 electrical channels, and the Omnetics interface 610 thereon can achieve very firm connection with the Omnetics pin interface 610 on the detection equipment.

[0097] The flat cable pad 62 is welded and fixed at the other end of the adapter circuit board 60, and the flat cable pad 62 can be electrically connected with the lead-out pad 5 at the rear end of the electrode main body 1. In one embodiment, the flat cable pad 62 is about 3 millimeters long and 100 microns wide, and has the same size or close size as the lead-out pad 5.

[0098] To achieve electrical connection of the flat cable pad 62 with the lead-out pad 5, as shown in Figure 8 , in this embodiment, the lead-out pad 5 and the flat cable pad 62 are arranged opposite to each other, and the lead-out pad 5 and the flat cable pad 62 are electrically connected through an anisotropic conductive film 7, so that the metal wiring 11 on the lead-out pad 5 and the flat cable pad 62 are electrically interconnected in the vertical direction.

[0099] Specifically, in the embodiment, the anisotropic conductive film 7 enables the vertical electrical connection of the flat cable pad 62 and the lead-out pad 5 under the action of heat and pressure, while maintaining the insulation in the horizontal direction, so that one-to-one connection of each channel on the electrode and the circuit on the adapter circuit board 60 can be achieved. After the anisotropic conductive film 7 is fixed on the flat cable pad 62, the lead-out pad 5 and the flat cable pad 62 are aligned under a microscope, and finally a hot press is used to realize the vertical electrical conduction of the two.

[0100] In one embodiment, as shown in Figure 9 The neural electrode further comprises an electrode shell 8, the adapter board is fixedly arranged in the electrode shell 8, and an electrode support platform 800 is arranged on the electrode shell 8, which supports the rear end of the electrode body 1.

[0101] Specifically, in the embodiment, the electrode shell 8 supports and protects the adapter board and the rear end of the electrode body 1. After implantation, the electrode shell 8 is located outside the tissue, the adapter board is fixedly arranged 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 adapter portion 102 at the rear end of the electrode body 1.

[0102] In one specific embodiment, as shown in Figures 9 to 11 The electrode shell 8 comprises a first fixed shell 80 and a second fixed shell 81.

[0103] The first fixed shell 80 is provided with limiting side walls 801 on both sides, the adapter circuit board 60 is arranged on the first fixed shell 80 and located between the limiting side walls 801 on both sides, the electrode support platform 800 is arranged on the first fixed shell 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 shell 81 is detachably fixed on the first fixed shell 80, and the inner side of the second fixed shell 81 is provided with a pressing beam 812 which is pressed on the adapter circuit board 60.

[0105] In the embodiment, the electrode shell 8 comprises a first fixed shell 80 as a lower shell and a second fixed shell 81 as an upper shell. The first shell is provided with limiting side walls 801 on both sides, so that the upper end of the first shell forms a through slot, and the mounting space is formed between the limiting side walls 801 on both sides, and the adapter circuit board 60 can be mounted in the mounting space, and the adapter circuit board 60 is limited by the limiting side walls 801 on both sides. At the same time, the first shell forms a through slot, and the opening at the rear end is convenient for connecting the adapter plug-in board 61 with the external detection equipment, and the opening at the front end is convenient for mounting the rear end of the electrode main body 1. The electrode support table 800 is a boss formed at the front end of the first shell, and the height of the electrode support table 800 is the same as the thickness of the adapter circuit board 60, so that the rear end of the electrode main body 1 is supported by the electrode support table 800, and the rear end of the electrode main body 1 can be kept on the same horizontal plane as the adapter circuit board 60, so that the electrode main body 1 and the electrode shell 8 can be kept parallel, and the accuracy of the implantation position in the operation is ensured.

[0106] The first fixed shell 80 and the second fixed shell 81 can be connected in a top-down buckle 810 manner. Specifically, as shown in Figure 10 , the side walls extending downward can be arranged on both sides of the second fixed shell 81, and the buckles 810 are formed by protruding horizontally at the lower end of the side walls. When installing, the second fixed shell 81 is installed from top to bottom on the first fixed shell 80, the side walls of the second fixed shell 81 are located outside the limiting side walls 801 of the first fixed shell 80, and the buckles 810 at the lower end of the second fixed shell 81 are buckled on the lower end surface of the first fixed shell 80.

[0107] Specifically, in the embodiment, the electrode support table 800 is used to support the connecting part 102 of the rear end of the electrode main body 1, and the expansion part 101 of the rear end of the electrode main body 1 corresponds to the upper and lower wire pads 62.

[0108] Further, as shown in Figure 9 , the upper end of the second fixed shell 81 is provided with a tube fixing structure 811;

[0109] The neural electrode further comprises a rubber tube 92, a connecting tube 91 and a connecting pipe 90, and the connecting tube 91 is an L-shaped pipe; the rubber tube 92 is detachably fixedly connected with the tube fixing structure 811, the first end of the connecting tube 91 is fixedly connected with the rubber tube 92, the second end of the connecting tube 91 is fixedly connected with the connecting pipe 90, and the lower end of the connecting pipe 90 is fixedly sleeved on the connecting column 4.

[0110] Specifically, in the embodiment, the lower end of the connecting tube 91 is fixedly connected with the connecting pipe 90, and the two are sealed by interference fit. The connecting tube 91 is 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, facilitating the connection of various devices. The upper end of the connecting tube 91 is connected with the rubber tube 92, and the rubber tube 92 is fixedly connected with the pipe fixing structure 811 horizontally. Specifically, the rubber tube 92 can be inserted and fitted with the pipe fixing structure 811, and fixed by the corresponding buckle 810.

[0111] In an embodiment, the rubber tube 92 is a medical silicone tube 92, and the connecting tube 91 can be an L-shaped metal tube. In order to facilitate the installation and disassembly of the rubber tube 92, a through installation groove can be provided on the pipe fixing structure 811, which is an arc-shaped groove, and the rubber tube 92 can be clamped and fixed in the installation groove.

[0112] In order to better fix the adapter circuit board 60, as shown in Figure 8 and Figure 10 , a positioning column 802 is arranged on the first fixing shell 80 in the embodiment, and a positioning hole 600 is arranged on the adapter circuit board 60, which is inserted and fitted with the positioning column 802. The positioning column 802 can be provided as a plurality of, and the positioning hole 600 can also be provided as a plurality of corresponding.

[0113] According to another aspect of the present application, a neural electrode preparation method is provided for preparing the neural electrode, and the neural electrode preparation method comprises the following steps:

[0114] Preparation of the electrode layer;

[0115] Forming the microfluid channel 2 on the surface of the electrode layer by 3D printing;

[0116] Processing the electrode layer to obtain the electrode body 1 conforming to the designed shape.

[0117] In the embodiment, the microfluid channel 2 is formed by 3D printing, which can realize the customized preparation of the neural electrode. The processing of the electrode layer includes processing the prepared electrode layer by cutting and etching to obtain the electrode body 1 conforming to the designed shape.

[0118] In an embodiment, in order to improve the preparation accuracy of the electrode layer, the preparation of the electrode layer comprises:

[0119] Depositing a sacrificial layer on the substrate. Specifically, 10 nanometers of titanium and 500 nanometers of aluminum can be deposited on a silicon wafer substrate as a sacrificial layer for release by using a magnetron sputtering method.

[0120] A bottom layer is formed on the sacrificial layer using a biocompatible material. Specifically, a 4-6 micron thick layer of polyimide is spin-coated on the sacrificial layer as the bottom layer.

[0121] The bottom layer is patterned using a photolithography process. Specifically, photoresist is spin-coated on the bottom layer, and then a photolithography and development process is performed to process the photoresist into the same shape as the substrate 10, and then a reactive ion etching process is performed to transfer the pattern to the bottom layer. At this point, the bottom layer has the same shape as the substrate 10 in the designed neural electrode structure, and the bottom layer is equivalent to the substrate 10 in the neural electrode structure.

[0122] The metal wiring 11 is formed on the bottom layer using a photolithography process and a metal deposition process. Specifically, the photoresist remaining after etching is removed using acetone, photoresist is spin-coated again, and then a photolithography and development process is performed to process the photoresist into the same shape as the metal wiring 11. A metal is deposited using a magnetron sputtering deposition method, and after deposition, the photoresist is removed using acetone. The conductive pattern on the bottom layer, which is the metal wiring 11, is obtained. It can be understood that when the metal wiring 11 includes multiple metal layers in the above embodiments, 10 nanometers of titanium, 50 nanometers of platinum, and 50 nanometers of gold are sequentially deposited during magnetron sputtering deposition to form the first metal layer 110, the second metal layer 111, and the third metal layer 112, respectively.

[0123] An insulating intermediate layer is formed on the bottom layer using a biocompatible material, and the back end of the metal wiring 11 is exposed on the bottom layer to form the lead-out pad 5. Specifically, poly-p-xylene is deposited using chemical vapor deposition to form the intermediate layer. At this point, the intermediate layer is not patterned, 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 the function and position of the intermediate layer are the same as those of the insulating layer 13. In subsequent processing, the intermediate layer can be processed by cutting to obtain the insulating layer 13 with the designed shape.

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

[0125] The support layer 14 is formed on the intermediate layer using a photolithography process and a deposition process, and the support layer 14 is patterned. Specifically, before the intermediate layer is processed by cutting, a magnetron sputtering deposition method is used to sequentially deposit 10 nanometers of titanium and 50 nanometers of copper as an electroplating seed layer on the intermediate layer. Photoresist is spin-coated again, and then a photolithography and development process is performed to process the photoresist into the same shape as the nickel support layer 14. A direct current electroplating method is used to electrodeposit about 15 microns of nickel, and then the titanium and copper seed layer is selectively etched to obtain the patterned support layer 14. At this point, the shape of the obtained support layer 14 is consistent with the shape of the designed support layer 14.

[0126] When the neural electrode further comprises the reinforcing beam 3 and the connecting column 4, the microfluid channel 2, the reinforcing beam 3 and the connecting 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 microfluid channel 2, the reinforcing beam 3, the connecting column 4 and the support layer 14 further need to be covered with a protective layer, the electrode layer in the embodiment is processed to obtain the electrode body 1 conforming to the designed shape, including:

[0128] The protective layer is formed on the microfluid channel 2 and the support layer 14 by a deposition process. Specifically, chemical vapor deposition of poly-p-xylene can be used to cover the exposed microfluid channel 2, reinforcing beam 3, connecting column 4 and support layer 14. At this time, the protective layer and the insulating layer 13 are both unpatterned layer structures, so the protective layer and the intermediate layer need to be cut 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 electrolytic aluminum.

[0130] The electrical detection point 12 is formed on the first side of the electrode body 1. Specifically, the designed position can be installed, and the bottom layer and the first metal layer 110 (when including the first metal layer 110) of the electrode body 1 are processed by etching to form the electrical detection point 12.

[0131] Further, the following steps are included:

[0132] The adapter 6 is electrically connected with the lead-out pad 5. Specifically, the specific connection mode of the adapter 6 and the lead-out pad 5 is designed according to the specific structure thereof. In one embodiment, when the adapter 6 comprises the structure as described in the above embodiment, the wire bonding pad 62 in the adapter 6 is electrically interconnected in the vertical direction by the anisotropic conductive film 7 under the action of heat and pressure.

[0133] The adapter 6 is installed into the electrode shell 8, and the flow channel inlet of the microfluid channel 2 is communicated with the tube assembly 9. Specifically, the adapter 6 can be first installed on the first fixed shell 80, and then the rubber tube 92, the connecting thin tube 91 and the connecting tube 90 in the tube assembly 9 are sequentially arranged, the second fixed shell 81 is then buckled and fixed on the first fixed shell 80, and finally the rubber tube 92 in the tube assembly 9 is fixed in the mounting groove of the second fixed shell 81.

[0134] The above only describes the preferred embodiments of the present application and is not used to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A neural electrode with drug delivery capability, characterized in that, include: The electrode body has multiple electrical detection points at its insertion end, the electrical detection points being located on the first side of the electrode body, and lead-out pads at its connection end. A microchannel is provided on the second side of the electrode body. The front end of the microchannel extends to the intervention end of the electrode body and can be inserted into the tissue along with the intervention end. The front end of the microchannel is provided with a channel outlet, and the rear end of the microchannel is provided with a channel inlet. The electrode body includes a substrate and metal wiring. The metal wiring is disposed on the substrate, and multiple electrical detection points are provided on the substrate, through which a portion of the metal wiring is exposed. The metal wiring includes a first metal layer, a second metal layer, and a third metal layer stacked sequentially on the substrate. The area on the first metal layer corresponding to the electrical detection point is selectively removed, and a portion 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.

2. The neural electrode with drug delivery capability according to claim 1, characterized in that, The electrode body includes an insulating layer and a support layer. The substrate and the insulating layer are made of biocompatible materials. The insulating layer covers the metal wiring, and the support layer covers the insulating layer. The rear end of the metal wiring is exposed on the substrate and forms the lead-out pad. The microchannel is disposed on the support layer.

3. The neural electrode with drug delivery capability according to claim 2, characterized in that, The area on the first metal layer corresponding to the lead-out pad is selectively removed.

4. The neural electrode with drug delivery capability according to claim 2, characterized in that, The support layer is made of 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. The lead-out 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 connection portion, and the rear end of the support layer covers the insulating layer corresponding to the connection portion.

6. The neural electrode with drug delivery capability according to claim 5, characterized in that, The neural electrode also includes a reinforcing beam and a connecting column. The reinforcing beam is located at the position corresponding to the connection part of the support layer, and the connecting column is located on the reinforcing beam. The rear end of the microchannel passes through and communicates with the lower end of the connecting column.

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

8. The neural electrode with drug delivery capability according to claim 7, characterized in that, The neural electrode also includes an adapter electrically connected to the lead-out pad and used for electrical connection 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, and ribbon cable pads. The adapter plug and the ribbon cable pads are electrically connected to the first and second ends of the adapter circuit board, respectively. The two ends of the adapter plug are provided with multiple interfaces, and the ribbon cable pads are electrically connected to the lead-out pads.

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

11. The neural electrode with drug delivery capability according to claim 9, characterized in that, The neural electrode also includes an electrode housing, the adapter is fixed inside the electrode housing, and an electrode support platform is provided on the electrode housing, which supports the rear end of the electrode body.

12. The neural electrode with drug delivery capability according to claim 11, characterized in that, The electrode housing includes a first fixed housing and a second fixed housing; The first fixed housing has limiting sidewalls on both sides, the adapter circuit board is disposed on the first fixed housing and located between the limiting sidewalls on both sides, the electrode support platform is disposed 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 housing is detachably fixed to the first fixed housing, and a clamping beam is provided on the inner side of the second fixed housing, which clamps 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 housing is provided with a tube fixing structure; The neural electrode also includes a rubber tube, a connecting tube, and a connecting tube. The connecting tube is L-shaped. The rubber tube is detachably fixed to the tube fixing structure. The first end of the connecting tube is fixedly connected to the rubber tube, the second end of the connecting tube is fixedly connected to the connecting tube, and the lower end of the connecting tube is sleeved and fixed on the connecting post.

14. The neural electrode with drug delivery capability according to claim 12, characterized in that, The first fixed housing is provided with a positioning post, and the adapter circuit board is provided with a positioning hole, which is inserted and engaged with the positioning post.

15. A method for preparing a neural electrode, characterized in that, The method for preparing the neural electrode according to any one of claims 1 to 14 comprises the following steps: Prepare electrode layers; The microchannels are formed on the surface of the electrode layer using 3D printing. The electrode layer is processed to obtain the electrode body that conforms to the design shape.

16. The method for preparing a neural electrode according to claim 15, characterized in that, The preparation of the electrode layer includes: Deposit a sacrificial layer on the substrate; A biocompatible material is used to form the bottom layer on the sacrificial layer; The underlying layer is patterned using photolithography. Metal wiring is formed on the underlying layer using photolithography and metal deposition processes; An insulating intermediate layer is formed on the bottom layer using biocompatible materials, and the rear end of the metal wiring is exposed on the bottom layer to form lead-out pads.

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

18. The method for preparing a neural electrode according to claim 17, characterized in that, Processing the electrode layer to obtain the electrode body conforming to the design shape includes: A protective layer is formed on the microchannels and support layer using a deposition process; Cut the protective layer and intermediate layer according to the design shape; Separate 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, It also includes the following steps: Electrically connect the adapter to the lead-out pads; Install the adapter into the electrode housing and connect the flow channel inlet of the microchannel to the tube assembly; Secure the tube assembly to the electrode housing.

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