A method for fabricating a multi-layer integrated multi-modal implantable sensor

By employing a multi-layer integrated multimodal implantable sensor fabrication method, the problems of large sensor area and low integration have been solved, achieving sensor miniaturization and high-density integration, which is suitable for multi-signal detection in the medical and health field.

CN116327119BActive Publication Date: 2026-01-13AEROSPACE INFORMATION RES INST CAS
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Patent Information

Application Number
CN202310193612.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-02-23
Publication Date
2026-01-13
Estimated Expiration
2043-02-23

AI Technical Summary

Technical Problem

Existing multimodal sensors suffer from large area and low integration, making it difficult to meet the requirements of implantable designs and limiting their application in the medical and health field.

Method used

A multi-modal implantable sensor fabrication method with multi-layer integration is adopted. By fabricating multi-layer sensors and leads on a flexible substrate, and using a stepped interface and layered lead structure, the miniaturization and high-density integration of the sensor are achieved.

Benefits of technology

By reducing the sensor area to 4mm*8mm and the height to less than 300um, the volume is greatly reduced and the integration is improved. Furthermore, the FPC connector enables effective connection between each sensor and the signal processing unit, reducing manufacturing difficulty and increasing yield.

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Abstract

The application relates to a multilayer integrated multimodal implantable sensor manufacturing method and belongs to the technical field of physiological detection; the method solves the problem that the multimodal sensor in the prior art is mostly distributed in a planar mode, has a large area and low integration; the method comprises the following steps: providing a first flexible substrate; preparing a pressure sensor and corresponding lead wires on the first flexible substrate to obtain a first sensing layer; preparing a second flexible substrate on the first sensing layer, and preparing a non-exposed flexible sensor and corresponding lead wires on the second flexible substrate to obtain a second sensing layer; preparing a third flexible substrate on the second sensing layer, and preparing an exposed flexible sensor and corresponding lead wires on the third flexible substrate to obtain a third sensing layer; setting the first sensing layer, the second sensing layer and the third sensing layer into a stepped shape at an interface of the multimodal implantable sensor; and respectively exposing the lead wires of each layer at the steps of each layer to obtain the multimodal implantable sensor.
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Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of physiological signal detection, in particular to a multi-layer integrated multi-modal implantable sensor manufacturing method. BACKGROUND

[0002] Flexible electronics is to make electronic devices on flexible or ductile plastic, thin metal substrate, so that the material can be bent, folded, twisted, compressed, stretched or even deformed into any shape while maintaining photoelectric performance, reliability and integration. With the continuous breakthrough of conductive polymer research and the continuous optimization of flexible electronics manufacturing process, this emerging technology has shown wide application prospects in information, energy, medical, defense and other fields, expanding the application range of electronic technology. At present, China's flexible electronics industry is still in the initial stage of development, especially in the field of biological medicine, which has great development potential and is one of the important directions for the development of flexible electronics and information industry in the future.

[0003] Based on the characteristics of light, thin, flexible and small of flexible electronics, it is very suitable for many scenarios in the medical and health field that have high requirements for the volume, weight and integration of devices, such as the elderly, daily health management, sports training, etc. Specifically, by making chips and integrated circuits flexible and implanting miniature flexible devices into the human body, the detection of human physiological information can be realized without affecting human health and living habits, thereby assisting medical institutions, individual users and athletes in disease treatment, health management and training guidance. To meet the needs of implanting flexible sensors into the human body, miniaturization and integration of sensors are the new development trend in the future, but the current flexible sensors generally have problems such as large area and low integration, which restrict the development of flexible electronics technology.

[0004] Current research on multi-modal sensors mostly adopts a planar distribution method, which has problems such as large area and low integration, and it is difficult to meet the needs of implantable design, which significantly limits its application. Therefore, it is of great significance to study high-density integration technology of multi-modal sensors and explore a feasible design scheme that can realize miniaturization and miniaturization of sensors to meet the needs of multi-signal detection of implantable sensors, reduce implantation trauma and obtain more accurate signals. SUMMARY

[0005] In view of the above analysis, the present application aims to provide a multi-layer integrated multi-modal implantable sensor manufacturing method; solve the problem that the multi-modal sensor manufacturing method in the prior art cannot realize multi-layer structure, and the planar distribution method has problems such as large area and low integration.

[0006] The purpose of the present application is mainly realized through the following technical solutions:

[0007] This invention provides a method for fabricating a multi-layer integrated multimodal implantable sensor, comprising the following steps:

[0008] Provide a first flexible substrate;

[0009] A pressure sensor and corresponding lead wires are fabricated on the first flexible substrate to obtain the first sensing layer.

[0010] A second flexible substrate is fabricated on the first sensing layer, and a non-exposed flexible sensor and corresponding lead wire are fabricated on the second flexible substrate to obtain the second sensing layer.

[0011] A third flexible substrate is fabricated on the second sensing layer, and an exposed flexible sensor and corresponding lead wires are fabricated on the third flexible substrate to obtain the third sensing layer.

[0012] The first, second, and third sensing layers are arranged in a stepped shape at the interface of the multimodal implantable sensor; the lead wires of each layer are exposed at each step to obtain the multimodal implantable sensor.

[0013] Furthermore, the first flexible substrate comprises two symmetrical parts; the fabrication of the pressure sensor on the first flexible substrate includes:

[0014] Two pressure-sensitive membrane windows are patterned symmetrically on the first flexible substrate;

[0015] The upper and lower electrode plates of the pressure sensor are fabricated corresponding to the two pressure-sensitive membrane windows, and the lead wires of the pressure sensor are fabricated on the first flexible substrate.

[0016] The first flexible substrate is folded along the axis of symmetry so that the lower electrode plate is aligned and covers the upper electrode plate, and a pressure sensor film is added in the middle to form a pressure sensor.

[0017] Furthermore, the lead wire is configured as a curved shape of arbitrary shape;

[0018] The lead wires of each layer extend to the interface in their respective layers and are exposed at the stepped position at the interface.

[0019] Furthermore, conductive wires are fabricated on the second and third flexible substrates, including:

[0020] A layer of metallic chromium is deposited on the second flexible substrate and the third flexible substrate, respectively;

[0021] Solid metal conductors are fabricated on metallic chromium using photolithography patterning.

[0022] Alternatively, conductive liquid materials can be fabricated on metallic chromium using screen printing or inkjet printing processes.

[0023] Furthermore, the non-exposed flexible sensor includes a temperature sensor and a stress sensor;

[0024] The fabrication of a non-exposed flexible sensor on a second flexible substrate includes:

[0025] Temperature sensor material and stress sensor material are deposited on the second flexible substrate and patterned; or temperature sensor and stress sensor are fabricated on other substrates and transferred to the second flexible substrate by pattern transfer to complete the fabrication of temperature sensor and stress sensor.

[0026] Furthermore, the exposed sensor includes a potassium-sodium ion sensor, an oxygen partial pressure sensor, a neural electrode, and an electrical stimulator; the potassium-sodium ion sensor and the oxygen partial pressure sensor adopt an embedded probe design or a probe design with the sensitive layer protruding.

[0027] The fabrication process of the potassium-sodium ion sensor, which employs an embedded probe design, includes:

[0028] Three electrodes are fabricated on the third flexible substrate, including a potassium ion working electrode, a reference electrode, and a sodium ion working electrode;

[0029] Conductive nanomaterials are deposited above potassium ion working electrodes and sodium ion working electrodes, and potassium ion selective films and sodium ion selective films are coated on the conductive nanomaterials and then cured.

[0030] PVB material was deposited on top of the reference electrode and cured to complete the fabrication of the potassium-sodium ion sensor.

[0031] Furthermore, the fabrication process of the oxygen partial pressure sensor, which is an embedded probe design, includes:

[0032] On the third flexible substrate, a three-electrode system, including a working electrode, a counter electrode, and a reference electrode, is fabricated using a metal thin film deposition and lift-off process.

[0033] The oxygen partial pressure sensor was fabricated by depositing a proton-conducting solid material on top of the electrodes.

[0034] The fabrication process of the neural electrode and electrical stimulator includes:

[0035] On the third flexible substrate, electrodes of metal Pt or Ir are fabricated using deposition or metal thin film lift-off processes, and porous nano-conductive particles are deposited to complete the fabrication of the neural electrode and the electrical stimulator.

[0036] Furthermore, the fabrication process of the potassium-sodium ion sensor and the oxygen partial pressure sensor with the sensitive layer protruding probe design includes: extending the third flexible substrate, and fabricating the three electrodes of each sensor in the extended portion of the third flexible substrate using a deposition or metal thin film lift-off process;

[0037] The corresponding electrochemical sensitive layer and curing layer are deposited to fully encapsulate each electrode by a drop-dip method.

[0038] Furthermore, the flexible substrate is made of photolithographic materials and non-photolithographic materials;

[0039] For flexible substrates of photolithographic materials, patterning is performed using photolithography during material forming;

[0040] For flexible substrates that are not photolithographic, after spin coating the substrate material, patterning is performed using photoresist and then etching is carried out; or after protection with a hard mask, etching is performed using oxygen or argon.

[0041] Furthermore, the first flexible substrate, the second flexible substrate, and the third flexible substrate may use the same or different substrate materials;

[0042] The preparation of the second flexible substrate and the preparation of the third flexible substrate include:

[0043] Flexible substrate material is spin-coated twice on the first sensing layer and the second sensing layer, respectively;

[0044] The flexible substrate material is etched using an oxygen dry etching process to obtain a flat second flexible substrate and a third flexible substrate material.

[0045] The second and third flexible substrates are obtained by etching the flat surfaces of the second and third flexible substrates using a plasma etching method with an oxygen to carbon tetrafluoride volume ratio of 1:1.

[0046] The beneficial effects of this technical solution are:

[0047] 1. This invention integrates multiple physiological and biochemical sensors within a multilayer substrate material, employing a three-layer sensor structure. The first and third layers are open-type exposed sensors, capable of sensing quantities that communicate with the outside world, such as chemical quantities (potassium and sodium ions, oxygen) and physical quantities (electrophysiological electrodes, pressure sensors). The second layer is a non-exposed sensor, capable of monitoring physical quantities that do not require contact with the outside world, such as temperature sensors and stress sensors. Different flexible substrates can use the same or different flexible substrate materials. Using non-heterogeneous integration methods, a multilayer three-dimensional flexible sensor is formed under traditional MEMS processes.

[0048] 2. The conductive wires of this invention also adopt a layered structure, with no spatial or temporal overlap between the layers. These multiple, unconnected conductive wires extend to the flexible FPC connector. Through a flexible substrate opening process, the conductive wire interfaces are fully exposed, effectively connecting each sensor component to the signal processing unit via the FPC connector. This connection method, compared to traditional single-layer parallel wiring, eliminates the need for multi-layer wiring vias, thus reducing manufacturing difficulty and increasing yield.

[0049] 3. The sensor made using this invention can reduce its area from 2cm*3cm in a planar structure to 4mm*8mm, while its height is similar to that of a planar structure, both being less than 300um, which greatly reduces the size of the sensor and improves its integration.

[0050] Other features and advantages of the invention will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the invention. The objects and other advantages of the invention may be realized and obtained by means of the structures particularly pointed out in the written description, claims, and drawings. Attached Figure Description

[0051] The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. Throughout the drawings, the same reference numerals denote the same parts.

[0052] Figure 1 This is a schematic diagram illustrating the fabrication method of a multimodal implantable sensor according to an embodiment of the present invention;

[0053] Figure 2 This is a schematic diagram illustrating the connection between the implantable sensor and the external processor according to an embodiment of the present invention;

[0054] Figure 3 The pressure sensor fabrication process according to an embodiment of the present invention;

[0055] Figure 4 This is a schematic diagram of an exposed sensor with an embedded probe design according to an embodiment of the present invention.

[0056] Figure 5 This is a schematic diagram of the exposed sensitive layer protruding probe design according to an embodiment of the present invention;

[0057] Figure 6 This is a schematic diagram illustrating the exposure treatment of the lead wire at the stepped structure interface in an embodiment of the present invention. Detailed Implementation

[0058] Preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings, which form part of this application and are used together with the embodiments of the present invention to illustrate the principles of the present invention, but are not intended to limit the scope of the present invention.

[0059] This invention discloses a method for fabricating a multi-layer integrated multimodal implantable sensor. It employs a multi-layer ex vivo structure, where each flexible substrate layer can be made of different materials depending on the corresponding sensor type. The multimodal implantable sensor fabricated using this method features a large number of integrated sensing units, simple fabrication, no need for heterogeneous integration, and high integration density. Within a space of less than 1 square centimeter, at least two flexible pressure sensors, two shear force sensors, two oxygen partial pressure sensors, two sets of different potassium and sodium ion sensors, and 15 neural electrodes can be integrated (the neural electrodes can be used for neural signal acquisition or neural electrical stimulation, or, through time-division multiplexing, the same electrode can perform both electrical signal acquisition and neural electrical stimulation functions). The implantable sensor prepared by this method can be connected to an external processor (integrated circuit and wireless transmission circuit) via a corresponding multi-layer flexible printed circuit (FPC), such as... Figure 2 As shown, the implantable sensor, which integrates a multi-layer flexible substrate and multiple flexible sensing units, can be placed under the skin, in the cavities of internal organs, or in the cerebrospinal fluid above the cerebral cortex. It is connected to the signal processing front-end circuit through flexible FPC cables, nylon filaments, or other biocompatible flexible wires as insulation layers, and can monitor multiple parameters such as muscle temperature, muscle strength, electromyography, oxygen partial pressure, and electrolyte concentration.

[0060] This embodiment describes a method for fabricating a multi-layer integrated, multimodal implantable sensor, such as... Figure 1 As shown, it includes the following steps:

[0061] Step S1: Provide a first flexible substrate.

[0062] Specifically, for implantable sensors, the flexible substrate material needs to be a biocompatible organic material that is easy to fabricate using MEMS (photolithography, etching, etc.). Therefore, the main materials that can be used include PI, parylene, and SU-8. By selecting the ratio of different components, the elastic modulus of the material can be matched with that of human brain and skin tissue, making it compatible with the cerebral cortex and skin, and minimizing the damage to brain tissue and skin caused by implanted devices. In this embodiment, the thickness of the flexible substrate is 7-10 μm, and the area of ​​the multimodal sensor is 4 mm * 8 mm. In practical applications, its specific dimensions can be designed into flexible multimodal sensors of different sizes and shapes according to the actual situation of the patient's wound and disease type.

[0063] For flexible substrate materials, one type is inherently photolithographic, such as photolithographically lithographic PI (negative photoresist properties) and SU-8, while the other type is non-photolithographically lithographic, such as non-photolithographic PI and Parylene. For photolithographically lithographic flexible substrate materials, patterning can be achieved during material forming using photolithography, resulting in a more precise structure. For non-photolithographically lithographic substrate materials, etching is required after spin-coating each layer of substrate material. Before etching, patterning with photoresist and proper protection are necessary. If the line quality requirements are not high, a hard mask can be used for protection before etching with oxygen, carbon tetrafluoride, argon, or other gases.

[0064] In practical applications, the stiffness, Young's modulus, yield coefficient, and other mechanical parameters of the substrate material can be determined according to different application scenarios, thereby selecting appropriate substrate and lead wire materials and fabrication processes. When fabricating the first flexible substrate, a rigid substrate is required as a support plate for processing. Preferably, the support plate can be formed by silicon-deposited aluminum. After the multilayer multimodal sensor is fabricated, the aluminum is removed using electrochemical anodic etching, thereby allowing the flexible sensor to be peeled off from the support plate. In this embodiment, the first flexible substrate comprises two symmetrical parts; these two symmetrical parts are used to fabricate the upper and lower electrode plates of the pressure sensor, respectively.

[0065] Step S2: Fabricate a pressure sensor and corresponding lead wires on the first flexible substrate to obtain the first sensing layer.

[0066] Specifically, such as Figure 3 As shown, a pressure sensor is fabricated on a first flexible substrate, comprising:

[0067] Two pressure-sensitive membrane windows, symmetrically arranged on the left and right sides, are patterned on a first flexible substrate;

[0068] The upper and lower electrode plates of the pressure sensor are fabricated corresponding to the two pressure-sensitive membrane windows, and the lead wires of the pressure sensor are fabricated on the first flexible substrate.

[0069] After the multimodal implantable sensor is fabricated and peeled off from the support plate, the lower electrode plate of the first flexible substrate is folded downward along the symmetrical axis, so that the lower electrode plate is aligned and covered with the upper electrode plate, and a pressure sensor film is added in the middle to form a pressure sensor.

[0070] In practical applications, after preparing the first flexible substrate, a pressure-sensitive membrane window is first patterned on the first flexible substrate, and then a layer of gold is deposited as the electrode and lead wire of the pressure sensor. The method of this embodiment can fabricate piezoresistive and capacitive pressure sensors, both of which have upper and lower electrode plates and a middle pressure-sensitive layer. The upper and lower electrodes are completed simultaneously in this step. After removing the support plate, one side of the lower electrode plate is bent downwards to align and cover the other electrode, and a pressure sensor film is added in the middle to form the pressure sensor. The pressure sensor film in the two electrode plates is also made of flexible material. After each sensing layer is prepared, a patterned exposure treatment is required at the end of the lead wire. The exposed lead wire can be electrically connected to an FPC cable to transmit the pressure signal detected by the pressure sensor to an external processing circuit.

[0071] Step S3: Prepare a second flexible substrate on the first sensing layer, and prepare a non-exposed flexible sensor and corresponding lead wires on the second flexible substrate to obtain the second sensing layer.

[0072] Specifically, the first, second, and third flexible substrates of this invention can be made of the same or different substrate materials. During the fabrication of the flexible multilayer structure of the multimodal sensor in this embodiment, the layers can influence each other; for example, the surfaces of the first and second sensing layers of the sensor will form an uneven structure. Fabricating the sensor and leads on uneven surfaces can easily lead to open circuits and poor contact between the metal leads and the flexible substrate. To solve this problem, in fabricating the second and third flexible substrates, this embodiment first spin-coates a flexible substrate material, such as PI, twice onto the first and second sensing layers, and then uses oxygen etching to obtain a smooth upper surface of the sensing layer; on the other hand, plasma etching is used to treat the PI surface at 50W power, with an oxygen to carbon tetrafluoride volume ratio of 1:1. Through chemical reaction, various functional groups (hydroxyl groups) are formed on the PI surface, and through physical bombardment, tiny depressions are created on the surface, increasing the surface area and enhancing the bonding between the flexible substrate and the metal. In addition, taking advantage of the good adhesion between metallic chromium and PI substrate and other metals, a layer of metallic chromium is first deposited on the PI substrate, followed by the deposition of other metal conductors (such as gold, silver, platinum, etc.), to achieve a firm bond between the metal conductors and the flexible PI substrate; the conductors can be set as serpentine, arc, or other arbitrarily shaped curved patterns.

[0073] The non-exposed flexible sensor in this embodiment includes a temperature sensor and a stress sensor;

[0074] Fabricating a non-exposed flexible sensor on a second flexible substrate includes:

[0075] Temperature sensor material and stress sensor material are deposited and patterned on a second flexible substrate; or temperature sensor and stress sensor are fabricated on other substrates and transferred to the second flexible substrate by pattern transfer to complete the fabrication of temperature sensor and stress sensor.

[0076] Step S4: Prepare a third flexible substrate on the second sensing layer, and prepare an exposed flexible sensor and corresponding lead wires on the third flexible substrate to obtain the third sensing layer.

[0077] Specifically, a third flexible substrate and the corresponding lead wires for the exposed sensor are first fabricated on the second sensing layer using the aforementioned method. In this embodiment, the exposed sensor includes a potassium-sodium ion sensor, an oxygen partial pressure sensor, a neural electrode, and an electrical stimulator; wherein the potassium-sodium ion sensor and the oxygen partial pressure sensor can employ either an embedded probe design or a probe design with the sensitive layer protruding from it.

[0078] Preferably, the potassium-sodium ion sensor adopts an embedded probe design, and its fabrication process includes:

[0079] Three electrodes are fabricated on top of the third flexible substrate, including a potassium ion working electrode, a reference electrode, and a sodium ion working electrode.

[0080] Conductive nanomaterials are deposited above potassium ion working electrodes and sodium ion working electrodes, and potassium ion selective films and sodium ion selective films are coated on the conductive nanomaterials and then cured.

[0081] PVB material was deposited on top of the reference electrode and cured to complete the fabrication of the potassium-sodium ion sensor.

[0082] The fabrication process of the oxygen partial pressure sensor with an embedded probe design includes:

[0083] On a third flexible substrate, a three-electrode system, including a working electrode, a counter electrode, and a reference electrode, is fabricated using a metal thin film deposition and lift-off process.

[0084] The oxygen partial pressure sensor was fabricated by depositing a proton-conducting solid material on top of the electrodes.

[0085] The fabrication process of neural electrodes and electrical stimulators includes:

[0086] On a third flexible substrate, electrodes of metal Pt or Ir are fabricated using deposition or metal thin film lift-off processes, and porous nano-conductive particles are deposited to complete the fabrication of neural electrodes and electrical stimulators.

[0087] As a specific example, such as Figure 4As shown, in the embedded probe design, multiple types of sensors on the third sensing layer are located above the main structure. First, potassium and sodium ion sensor electrode materials are deposited and patterned on the fabricated third flexible layer. The working electrode can be Pt, and the reference electrode can be Ag / AgCl. Oxygen partial pressure sensor materials (such as Pt) are deposited and patterned. Simultaneously with Pt deposition, partial patterning can be performed to form multi-channel neural electrodes and electrical stimulation materials. Further, conductive nanomaterials, such as PEDOT:PSS, are deposited above the working electrode of the potassium and sodium ion sensor, covering both potassium and sodium ion selective films. These are then cured by mixing adhesives such as PVC and DOS to form solid potassium and sodium ion selective films. PVB material is deposited and cured above the ion sensor reference electrode to reduce baseline drift. For the oxygen partial pressure sensor, proton-conductive solid materials, such as Nafion, can be deposited above the electrode to form the oxygen partial pressure sensor sensitive film. For the neural electrodes and electrical stimulator, a layer of porous conductive nanoparticles, such as gold nanowires or platinum black, can be deposited to reduce their output impedance.

[0088] Furthermore, the potassium and sodium ion sensors and oxygen partial pressure sensors adopt a probe-type design with a protruding sensitive layer. The fabrication process includes: extending the third flexible substrate, and fabricating the three electrodes of each sensor on the extended part of the third flexible substrate using deposition or metal thin film peeling process; and depositing the corresponding electrochemical sensitive layer and curing layer to fully encapsulate each electrode by drop-dip coating.

[0089] It should be noted that the third sensing layer adopts a protruding probe design, where the potassium and sodium ion sensors and oxygen partial pressure sensors extend beyond the main structure of the multimodal sensor. Figure 5 As shown, the neural electrodes remain located above the main structure. The sensitive layer protruding probe design allows for the complete encapsulation of the electrochemical sensitive layer and its curing layer, such as PVC and DOS synthetic agents, via drop-dip deposition. This increases the adsorption area of ​​the sensitive layer, improves adsorption stability, and enhances the sensor's sensitivity.

[0090] Preferably, after the third sensing layer is fabricated, a fourth flexible layer can be covered on top of the third sensing layer. The flexible insulating layer area directly above the potassium-sodium ion sensor, oxygen partial pressure sensor, neural electrode, and electrical stimulator can be etched away by photolithography or a shadow mask to achieve the exposure treatment of the exposed sensor.

[0091] Step S5: Set the first sensing layer, the second sensing layer and the third sensing layer into a stepped shape at the interface of the multimodal implantable sensor; expose the lead wires of each layer at each step to obtain the multimodal implantable sensor.

[0092] Specifically, the multi-layer sensing layer of this invention employs a stepped structure design at the interface of the multi-modal sensor, which exposes the lead wires of each layer at the stepped position of the interface of that layer, such as... Figure 6 As shown, the advantage of the stepped structure design at the interface is that the lead wires of each layer do not need to be designed with a through-hole structure. They only need to extend to the interface at the current layer and reinforce the gold fingers at the interface position for exposure.

[0093] In this embodiment, lead wires are fabricated for each sensing layer to connect the interface between the sensor and the multimodal sensor in each layer. The lead wires can be designed in serpentine, arc, or any other curved shape to maintain electrical stability during substrate stretching or compression. If the lead wire density is high, a simple straight shape can also be chosen. Furthermore, based on the stepped structure design, the lead wires between layers do not overlap in time and space. Multiple layers of unconnected lead wires extend to the connector of the multimodal sensor. Through a flexible substrate opening process, the lead wire interfaces are fully exposed, effectively connecting each sensor component to the signal processing unit via an FPC connector. The lead wire design in this embodiment has the advantage of eliminating the need for multi-layer through-hole connections, thus reducing fabrication difficulty and significantly improving yield and signal quality.

[0094] In summary, the multi-layer integrated multimodal implantable sensor fabrication method provided by the embodiments of the present invention integrates multiple physiological and biochemical sensors within a multi-layer substrate material, employing a three-layer sensor structure. The first and third layers are open-exposed sensors, capable of sensing quantities that communicate with the outside world, such as chemical quantities (potassium and sodium ions, oxygen) and physical quantities (electrophysiological electrodes, pressure sensors). The second layer is a non-open-exposed sensor, capable of monitoring physical quantities that do not require contact with the outside world, such as temperature sensors and stress sensors. Each layer can utilize different flexible substrate materials, employing non-heterogeneous integration methods to form a multi-layered three-dimensional flexible sensor using traditional MEMS processes. Furthermore, the lead wire design of the present invention also adopts a layered structure, with no spatiotemporal overlap between layers. The multi-layered, unconnected lead wires extend to the connector portion of the multimodal sensor. Through a flexible substrate opening process, full exposure at the lead wire interface is achieved, thereby effectively connecting each sensor component to the signal processing unit via an FPC connector. The advantage of this connection method over traditional single-layer parallel routing is that it eliminates the need for multi-layer routing vias, thereby reducing manufacturing difficulty and improving yield and signal quality.

[0095] Those skilled in the art will understand that all or part of the processes of the methods described in the above embodiments can be implemented by a computer program instructing related hardware, and the program can be stored in a computer-readable storage medium. The computer-readable storage medium may be a disk, optical disk, read-only memory, or random access memory, etc.

[0096] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A method of fabricating a multi-layer integrated multi-modal implantable sensor, the method comprising: The method comprises the following steps: ​ providing a first flexible substrate; preparing a pressure sensor and corresponding lead wires on the first flexible substrate to obtain a first sensing layer; preparing a second flexible substrate on the first sensing layer, and preparing a non-exposed flexible sensor and corresponding lead wires on the second flexible substrate to obtain a second sensing layer; preparing a third flexible substrate on the second sensing layer, and preparing an exposed flexible sensor and corresponding lead wires on the third flexible substrate to obtain a third sensing layer; the lead wires are arranged in a curved pattern of any shape; the lead wires of each layer extend to an interface at the layer where they are located, and are exposed at a stepped position at the interface; the lead wires on the second and third flexible substrates are prepared by: depositing a layer of metal chromium on the second and third flexible substrates respectively; using a photolithography patterning process to prepare lead wires of solid metal material on the metal chromium; or using a screen printing or inkjet printing process to prepare lead wires of conductive liquid material on the metal chromium; the first, second and third sensing layers are arranged in a stepped shape at the interface of the multi-modal implantable sensor, and the lead wires of each layer are exposed at the steps of each layer respectively to obtain the multi-modal implantable sensor.

2. The method of claim 1, wherein, the first flexible substrate comprises two symmetrical parts; and the pressure sensor is prepared on the first flexible substrate by: patterning two left-right symmetrical pressure-sensitive film windows on the first flexible substrate; preparing upper and lower electrode plates corresponding to the two pressure-sensitive film windows, and preparing lead wires of the pressure sensor on the first flexible substrate; folding the first flexible substrate along the symmetry axis to align and cover the lower electrode plate with the upper electrode plate, and adding a pressure sensor film in the middle to form the pressure sensor.

3. The method of claim 1, wherein, the non-exposed flexible sensor comprises a temperature sensor and a stress sensor; the non-exposed flexible sensor is prepared on the second flexible substrate by: depositing temperature sensor material and stress sensor material on the second flexible substrate and patterning; or preparing the temperature sensor and the stress sensor on other substrates, and transferring them to the second flexible substrate by pattern transfer to complete the preparation of the temperature sensor and the stress sensor.

4. The method of claim 1, wherein, the exposed flexible sensor comprises a potassium-sodium ion sensor, an oxygen partial pressure sensor, a neural electrode and an electrical stimulator; the potassium-sodium ion sensor and the oxygen partial pressure sensor adopt an embedded probe type or a sensitive layer protruding probe type design; the preparation process of the potassium-sodium ion sensor adopting the embedded probe type design comprises: making three electrodes on the third flexible substrate, including a potassium ion working electrode, a reference electrode and a sodium ion working electrode; depositing conductive nanomaterial on the potassium ion working electrode and the sodium ion working electrode, covering a potassium ion selective film and a sodium ion selective film on the conductive nanomaterial and solidifying; depositing PVB material on the reference electrode and solidifying to complete the preparation of the potassium-sodium ion sensor.

5. The method of claim 4, wherein, the preparation process of the oxygen partial pressure sensor in the embedded probe type design comprises: On the third flexible substrate, three electrodes including working electrode, counter electrode and reference electrode are made by deposition of metal thin film stripping process; Proton conductive solid-state material is deposited above the electrodes to complete the preparation of oxygen partial pressure sensor; The preparation process of the neural electrode and the electrical stimulator includes: On the third flexible substrate, electrodes of metal Pt or Ir are made by deposition or metal thin film stripping process, and porous nano conductive particles are deposited to complete the preparation of neural electrode and electrical stimulator.

6. The method of claim 5, wherein, The preparation process of the potassium-sodium ion sensor and the oxygen partial pressure sensor with the sensitive layer protruding probe design includes: extending the third flexible substrate, and making three electrodes of each sensor on the extended part of the third flexible substrate by deposition or metal thin film stripping process; The corresponding electrochemical sensitive layer and solidification layer are deposited on each electrode by dipping method.

7. The method of claim 1, wherein, The material of the flexible substrate includes photoetchable material and non-photoetchable material; For the flexible substrate of photoetchable material, patterning is performed by photoetching technology when the material is formed; For the flexible substrate of non-photoetchable material, after the substrate material is spin-coated, patterning is performed using photoresist, and etching is performed; or after protection by hard mask, etching is performed using oxygen or argon.

8. The method of claim 7, wherein, The first flexible substrate, the second flexible substrate and the third flexible substrate use the same or different substrate materials; The preparation of the second flexible substrate and the third flexible substrate includes: The flexible substrate material is spin-coated twice on the first sensing layer and the second sensing layer respectively; The flexible substrate material is etched by oxygen dry method to obtain flat second flexible substrate and third flexible substrate material; The surface of the flat second flexible substrate and third flexible substrate material is etched by plasma etching method according to the component ratio of oxygen to carbon tetrafluoride of 1:1 to obtain the second flexible substrate and the third flexible substrate.

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