Self-forming flexible bioelectronic device based on metal film stress regulation and control and preparation method of self-forming flexible bioelectronic device

Abstract

The invention discloses a self-forming flexible bioelectronic device based on metal film stress regulation and control and a preparation method of the self-forming flexible bioelectronic device. The preparation method comprises the following steps: S1, providing a rigid temporary substrate; s2, forming a first flexible packaging layer on the rigid temporary substrate; s3, depositing a metal functional thin film layer on the first flexible packaging layer through a physical vapor deposition process to form intrinsic stress of a preset type and a preset size in the thin film layer; s4, forming a second flexible packaging layer on the metal functional thin film layer; and S5, separating the first flexible packaging layer from the rigid temporary substrate to obtain the self-forming flexible bioelectronic device. The final shape of the device can be controlled by regulating and controlling a single process parameter, the controllability of the shape is realized, and the method is particularly suitable for preparing an implantable neural interface; the method is simple in process and completely compatible with a standard micromachining technology, and a solution is provided for batch manufacturing of high-performance customized three-dimensional flexible electronic devices.

Description

Technical Field

[0001] This invention relates to the fields of biomedical engineering technology, medical device technology, and micro-nano fabrication technology. Specifically, it relates to a self-forming flexible bioelectronic device based on metal thin film stress regulation and its fabrication method. Background Technology

[0002] With the deep integration of flexible electronics and biomedicine, the development of flexible bioelectronic devices capable of bending or conformal contact with biological tissues has become a research hotspot. Especially for implantable devices targeting complex curved tissues such as the brain, nerves, and heart, the three-dimensional configuration of the device directly affects its biocompatibility, interface stability, and functional effectiveness. However, this hybrid material system of flexible bioelectronic devices faces challenges such as the mismatch between processing technology requirements and material properties.

[0003] Based on a search of existing technologies, Liu Y. et al. published an article in Nature Neuroscience titled "A high-density 1,024-channel probe for brain-wide recordings in non-human primates," which achieved a high-density, deep-brain activity recording pathway by rolling a flexible planar neural electrode array onto a tungsten wire to form a tight vortex. However, the rolling process in this design is currently done manually, limiting scalability. Yu M. et al. published an article in ACS Applied Materials & Interfaces titled "Self-Closing Stretchable Cuff Electrodes for Peripheral Nerve Stimulation and Electromyographic Signal Recording," reporting that the cuff electrodes rely on the mechanical stress mismatch between different layers of an elastic base to achieve rolling, enabling them to wrap tissue bundles without additional mechanical locking structures. However, the reported fabrication process uses high-temperature annealing, which is not suitable for inelastic, ultra-thin, and heat-sensitive flexible substrates, nor is it suitable for high-precision micro-nano fabrication processes, thus limiting its practical application. Summary of the Invention

[0004] To overcome the shortcomings of existing technologies, this invention provides a self-forming flexible bioelectronic device based on metal thin film stress modulation and its fabrication method. This method involves depositing a functional metal layer on a flexible insulating substrate. By modulating the intrinsic stress generated in the functional layer during deposition, the stress becomes the driving force for the self-forming of the entire flexible device. After release, it autonomously curls into a predetermined three-dimensional structure, thus realizing a flexible bioelectronic device with morphology controllable and requiring no external force for assembly.

[0005] The technical solution of the present invention is described in detail below.

[0006] This invention provides a method for fabricating a self-forming flexible bioelectronic device based on metal thin film stress modulation, comprising the following steps: S1: Provide a rigid temporary substrate; S2: A first flexible encapsulation layer is formed on the rigid temporary substrate; S3: On the first flexible encapsulation layer, a metal functional thin film layer is deposited by physical vapor deposition process. The material of the metal functional thin film layer is a biocompatible metal or alloy. In this process, by adjusting the key parameters in the physical vapor deposition process, an intrinsic stress of a preset type and preset size is formed inside the metal functional thin film layer. S4: A second flexible encapsulation layer is formed on the functional thin film layer, and the fabrication of the electronic device is completed; S5: Separate the first flexible encapsulation layer from the rigid temporary substrate to obtain a self-forming flexible bioelectronic device; wherein, the preset intrinsic stress of the metal functional thin film layer drives the flexible bioelectronic device to spontaneously transform from a two-dimensional planar structure to a preset three-dimensional spatial structure.

[0007] In this invention, in step S1, the rigid temporary substrate is silicon, glass, or quartz substrate; in steps S2 and S4, the first flexible encapsulation layer and the second flexible encapsulation layer are independently selected from parylene, polyimide PI, polydimethylsiloxane PDMS, polyethylene terephthalate PET, SU-8 photoresist, or their composite materials, with a thickness of 0.1 micrometer to 10 micrometers, and correspondingly selected by spin coating curing or chemical vapor deposition method; in step S3, the metal functional thin film layer material is gold Au, platinum Pt, gold-platinum Au-Pt alloy, or platinum-iridium Pt-Ir alloy, with a thickness of 10 nanometers to 500 nanometers.

[0008] In this invention, in step S3, the physical vapor deposition process is magnetron sputtering, and the key parameter is sputtering pressure. During magnetron sputtering, the intrinsic stress of the metal functional thin film layer is continuously controlled to change between compressive and tensile stress by adjusting the sputtering pressure. The intrinsic stress ranges from -1 to 1 gigapascal, and the sputtering pressure ranges from 0.1 pascal to 5 pascal.

[0009] In this invention, in step S3, there exists a critical pressure; when the sputtering pressure is lower than the critical pressure, the functional thin film layer forms compressive stress; when the sputtering pressure is higher than the critical pressure, tensile stress is formed; when the sputtering pressure reaches the critical pressure, neutral stress is formed; the range of the critical pressure is 0.4-4 Pascals; the range of the neutral pressure is -20 to 20 MPa.

[0010] In this invention, step S3 further includes the following process parameters for magnetron sputtering: a vacuum level of 5 × 10⁻⁶. -4 Below Pascal, the purity of the metal target is above 99.99%, the substrate temperature is between 10-60℃, and the sputtering rate is 10-500 nm / min.

[0011] In this invention, in step S5, the device contour is separated by laser, chemical or plasma etching methods to achieve the separation of the first flexible packaging layer from the rigid temporary substrate.

[0012] The present invention also provides a self-forming flexible bioelectronic device prepared by the above-described method, comprising a first flexible encapsulation layer, a functional thin film layer having a preset pattern, and a second flexible encapsulation layer stacked sequentially; the functional thin film layer has a preset intrinsic stress, which enables the composite film system consisting of the first flexible encapsulation layer, the functional thin film layer and the second flexible encapsulation layer to spontaneously maintain a stable three-dimensional configuration in a self-supporting state.

[0013] In this invention, the functional thin film layer has a preset intrinsic stress, and the functional thin film will not break or be damaged due to the intrinsic stress; the intrinsic stress ranges from -1 to 1 gigapascal.

[0014] In this invention, by designing the pattern of the functional thin film layer and the spatial distribution of the preset intrinsic stress, the self-forming flexible bioelectronic device is selected from one or a combination of the following forms: (a) Self-curling probe: The functional thin film layer is a uniform compressive stress layer, which makes the device curl into a tubular or needle-like structure; it is suitable for implantable recording / stimulation of deep brain tissue, muscles and other target points; (b) Self-encapsulating probe: The functional thin film layer is a uniform tensile stress layer, which allows the device to be rolled into a sleeve structure that can encapsulate biological tissues, such as nerves, blood vessels or muscle bundles.

[0015] (c) Conformal planar array: The functional thin film layer is a near-neutral stress layer, which enables the device to conform to the curved surface of biological tissue, such as a planar flexible structure that can conform to the cerebral cortex and the surface of the heart.

[0016] In this invention, the morphology of the self-forming flexible bioelectronic device can also be: (d) Complex curved surface array: The functional thin film layer is patterned in a regionalized manner by photolithography, and different deposition parameters are applied to different regions (such as mask partition deposition) to introduce differentiated stress distribution within a single device, thereby achieving more complex three-dimensional deformations, such as saddle shape, spiral shape, etc., to match specific anatomical structures. (e) Multilayer heterostructure: Repeat steps S2 to S4 to deposit and pattern multiple functional thin films with different stress states to construct a complex three-dimensional electronic system capable of multi-level deformation such as segmented bending and stepped folding.

[0017] Furthermore, the present invention provides an application of the above-mentioned self-forming flexible bioelectronic device as a neural interface, wherein the neural interface includes a deep brain probe, a cortical electrode array, or a peripheral nerve cuff electrode.

[0018] Furthermore, the present invention also provides a neural interface system comprising the above-described self-forming flexible bioelectronic device and a signal processing unit electrically connected to the circuit pattern of the device.

[0019] Compared with the prior art, the present invention has the following beneficial effects: 1. Shape controllability: By adjusting a single, easily controllable sputtering parameter (gas pressure), the final three-dimensional shape of the device can be precisely preset, realizing a controllable transformation from a planar shape to a curled structure of different diameters (according to the Stony formula, the greater the stress, the smaller the diameter of the curled structure), without the need for complex micro-machining or manual assembly.

[0020] 2. Good process compatibility: The entire fabrication process is fully compatible with standard micromachining processes, easy to integrate with existing integrated circuit processes, and suitable for mass production.

[0021] 3. Simple structure and reliable performance: The device has a multilayer thin-film structure, requiring no external driving components or biodegradable materials. The metal thin film is dense, the electrode performance is stable, and the structure formed by stress self-rolling has good consistency.

[0022] 4. Material properties and functions are not damaged: The stress conditioning process does not introduce post-processing steps such as high-temperature annealing that may damage the properties of the material or substrate.

[0023] 5. Wide range of applications: This method is universal. Based on the same planar processing platform, multifunctional neural interfaces can be directly fabricated by changing the stress of the metal layer. It can also be widely used in wearable sensors, flexible energy storage devices, microrobots, and any other flexible microsystems that require transformation from planar to three-dimensional.

[0024] Based on the stress modulation strategy, controllable bending of ultrathin planar bioelectronic interfaces can be achieved. For ultrathin flexible electronic devices, this invention achieves continuous stress modulation from compressive to tensile stress by adjusting a single deposition parameter of the metal film—the sputtering gas pressure—during the magnetron sputtering deposition process. The stress gradient determines the bending direction and curvature of the flexible device after release. This method does not damage the material, requires no pre- or post-treatment, and integrates seamlessly with standard micro / nano fabrication processes. Based on this mechanism, the designed and fabricated self-forming flexible bioelectronic device meets the demands for miniaturization, integration, intelligence, and mass production of modern bioelectronic devices. Attached Figure Description

[0025] Figure 1 This is a schematic diagram illustrating the principle of a stress-modulated self-forming flexible bioelectronic device.

[0026] Figure 2 The stress diagrams for the gold-platinum alloy under different sputtering pressures in the examples are shown.

[0027] Figure 3 The stress diagrams are shown for the three-layer structure thin films of gold-platinum alloy under different sputtering pressures in the examples.

[0028] Figure 4 The images shown are scanning electron microscope images of the gold-platinum alloy under different stress states in the examples.

[0029] Figure 5 The images shown are atomic force microscope images of the gold-platinum alloy under different stress states in the embodiments.

[0030] Figure 6 The images show X-ray diffraction patterns of the gold-platinum alloy under different stress states in the examples.

[0031] Figure 7 The X-ray photoelectron spectra of gold-platinum alloys under different stress states are shown in the examples.

[0032] Figure 8 Optical photographs of three typical self-forming neural interfaces prepared in the examples: (A) self-coiled deep brain tubular electrode, (B) conformal cortical array, and (C) self-encapsulating peripheral nerve sleeve electrode.

[0033] Figure 9 The following are verification diagrams of the electrochemical and electrophysiological performance of the devices in the examples: (A) Electrochemical impedance spectroscopy, (B) Acute in vivo recorded neurophysiological signals. Detailed Implementation

[0034] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0035] This invention provides a method for fabricating a self-forming flexible bioelectronic device based on metal thin film stress modulation. The core of this method lies in: on a flexible encapsulation layer, by adjusting the physical vapor deposition process parameters, to create an intrinsic stress of a predetermined type and magnitude that is continuously adjustable within the deposited functional metal thin film layer, such as… Figure 1 As shown. When the device is released from the rigid temporary substrate, the stress acts as an intrinsic driving force, causing the entire multilayer thin film structure to spontaneously transform from a two-dimensional planar state to a preset three-dimensional spatial configuration, such as a tubular probe, sleeve, or conformal planar structure.

[0036] Example 1: Preparation of a self-curling deep brain probe This embodiment provides a specific preparation process for a self-curling deep brain probe based on Parylene-C and a gold-platinum alloy: Step 1: Substrate preparation. A 4-inch silicon wafer is used as a rigid temporary substrate.

[0037] Step 2: Deposit the lower encapsulation layer. Using the Parylene deposition system, a 2.0-micron-thick Parylene-C film is deposited on the silicon wafer as the first flexible encapsulation layer according to standard process parameters.

[0038] Step 3: Deposit a stress-tunable functional layer. Transfer the sample into a magnetron co-sputtering system (base vacuum reduced to 5 × 10⁻⁶). -4 Below Pascal. Pure gold (99.999%) and pure platinum (99.99%) targets were used. High-purity argon (99.999%) was introduced, and the working pressure was precisely set to 0.6 Pascal using a mass flow controller. The RF power of the gold and platinum targets was set to 200 watts and 150 watts, respectively, with the reflected power less than 10% of the corresponding incident power. The substrate stage rotated at 10 revolutions per minute without active heating. Deposition was performed under these conditions for 300 seconds, resulting in a gold-platinum alloy film with a thickness of 200 ± 10 nm. According to previous calibrations, the film deposited at this pressure exhibits compressive stress (approximately -300 MPa).

[0039] Step 4: Patterning the functional layer. Using photolithography and lift-off processes, the metal thin film is patterned into a circuit pattern containing circular electrode contacts, leads, and bonding points with a diameter of 100 micrometers.

[0040] Step 5: Deposit the encapsulation layer and expose the contacts. Using the Parylene deposition system again, a 2.0-micron-thick Parylene-C layer is deposited on the patterned device as a second encapsulation layer. Subsequently, oxygen plasma reactive ion etching is used to precisely create windows in the area directly above the electrode contacts, exposing the contact surface.

[0041] Step 6: Release and Self-Shaping. The device edges were separated using a laser and then immersed in deionized water, allowing the entire flexible device to be completely peeled from the silicon wafer. Upon release from constraint, the device immediately stabilized and formed a tightly packed tubular probe due to the compressive stress of the metal layer. The electrode contacts were located on the outer side of the tube wall. Acute implantation experiments were performed in the rat brain, successfully recording clear stimulus-evoked local field potentials.

[0042] Example 2: Fabrication of a planar conformal cerebral cortex array The steps are basically the same as in Example 1, with the key difference being: In step 3, the sputtering working pressure is precisely adjusted to 0.71 Pascals (reaching the critical pressure under the conditions of this equipment, which has been determined through prior testing). Other parameters remain unchanged. The film stress after deposition is close to zero (average stress approximately +5 MPa).

[0043] After release in step 6, the device maintained excellent planarity and showed no spontaneous curling tendency. When placed on the rat cerebral cortex, the device perfectly conformed to the curved surface due to its flexibility. Acute implantation experiments in the rat brain successfully recorded clear stimulus-evoked local field potentials.

[0044] Example 3: Fabrication of self-encapsulating peripheral nerve cuff electrodes The steps are basically the same as in Example 1, with the key difference being: In step 3, the sputtering working pressure is precisely adjusted to 0.8 Pascals. Under this condition, the film generates significant tensile stress (approximately +400 MPa).

[0045] After release in step 6, the device rapidly curls towards the metal layer, forming a sleeve electrode. This sleeve is then placed over the rat's sciatic nerve, achieving stable coverage without the need for sutures. Clear neural complex action potentials are recorded.

[0046] Example 4: Spatial Selective Stress Control (Complex Surfaces) This embodiment demonstrates how to achieve differentiated stress distribution within the same device.

[0047] In step 3, during the deposition of the functional layer, a specially designed mask is used to cover a portion of the sample. First, partial areas (regions 1 and 2) are deposited at a pressure of 0.6 Pa. Then, the mask is moved to cover region 1, exposing only regions 2 and 3. The chamber pressure is then increased to 0.7 Pa, and a thin layer is deposited. Thus, region 1 is a compressive stress layer, region 2 is a low-stress layer, and region 3 is a zero-stress layer.

[0048] After the device is released, region 1 curls uniformly toward the first encapsulation layer, region 2 forms a gentle bending transition, and region 3 remains planar. This results in a gradient three-dimensional structure that transitions from tight curling to gentle bending, which can be used to connect structures with different curvatures.

[0049] Figure 2 The stress variation trend of gold-platinum alloy sputtered on Parylene with sputtering pressure is shown. It can be observed that 0.71 Pascal is the critical pressure, and the metal film undergoes a continuous change from compressive stress to tensile stress.

[0050] Figure 3 The stress variation trend of flexible electronic thin films based on sputtered gold-platinum alloy with sputtering gas pressure is shown. It can be observed that the flexible thin film undergoes a continuous change from compressive stress to tensile stress under the influence of the stress change of the metal thin film.

[0051] Figure 4 and Figure 5 The surface morphology of the metal thin film was shown, demonstrating the changes in grain structure and surface roughness of the metal under different sputtering pressures, and verifying the stress changes of the metal thin film.

[0052] Figure 6 and Figure 7 The chemical composition of the metal thin film was shown, demonstrating the changes in chemical composition and crystal form of the metal under different sputtering pressures. For alloy materials, changes in gas pressure conditions affect the chemical composition of the alloy.

[0053] Figure 8 The application of the flexible electronic devices in Examples 1-3 in biological organisms demonstrates the effect of sputtering pressure control in the deposition process to achieve the curling from the first encapsulation layer to the second encapsulation layer.

[0054] Figure 9 The working effect of the flexible electronic devices in Examples 1-3 in a living organism is demonstrated, and it is verified that the curling of the flexible device by utilizing the stress of the functional layer does not affect the function of the device.

[0055] As can be seen from the above embodiments, this invention utilizes a stress-controlled self-forming flexible bioelectronic device and its fabrication method. The internal stress of the deposited functional layers drives the entire multilayer thin-film structure to spontaneously transform from a two-dimensional planar state to a predetermined three-dimensional spatial configuration. This method is simple in process and fully compatible with standard microfabrication techniques, making it possible to mass-produce customized three-dimensional bioelectronic devices on wafers. This will not only accelerate the development of neuroscience research and brain-computer interface technology but also provide technical support for future implantable diagnostic and therapeutic applications and flexible robotics.

[0056] Although the present invention has been described in detail through the preferred embodiments above, it should be understood that the above description should not be considered as a limitation of the present invention. Various modifications and substitutions to the present invention will be apparent to those skilled in the art after reading the above description. Therefore, the scope of protection of the present invention should be defined by the appended claims.

Claims

1. A method for fabricating a self-forming flexible bioelectronic device based on metal thin film stress modulation, characterized in that, Includes the following steps: S1: Provide a rigid temporary substrate; S2: A first flexible encapsulation layer is formed on the rigid temporary substrate; S3: On the first flexible encapsulation layer, a metal functional thin film layer is deposited by physical vapor deposition process. The material of the metal functional thin film layer is a biocompatible metal or alloy. In this process, by adjusting the key parameters in the physical vapor deposition process, an intrinsic stress of a preset type and preset size is formed inside the metal functional thin film layer. S4: A second flexible encapsulation layer is formed on the functional thin film layer, and the fabrication of the electronic device is completed; S5: Separate the first flexible encapsulation layer from the rigid temporary substrate to obtain a self-forming flexible bioelectronic device; wherein, the preset intrinsic stress of the metal functional thin film layer drives the flexible bioelectronic device to spontaneously transform from a two-dimensional planar structure to a preset three-dimensional spatial structure.

2. The preparation method according to claim 1, characterized in that, In step S1, the rigid temporary substrate is silicon, glass, or quartz substrate; in steps S2 and S4, the first flexible encapsulation layer and the second flexible encapsulation layer are independently selected from parylene, polyimide PI, polydimethylsiloxane PDMS, polyethylene terephthalate PET, SU-8 photoresist, or their composite materials, with a thickness of 0.1 micrometer to 10 micrometers, and correspondingly selected by spin coating curing or chemical vapor deposition method; in step S3, the metal functional thin film layer material is gold Au, platinum Pt, gold-platinum Au-Pt alloy, or platinum-iridium Pt-Ir alloy, with a thickness of 10 nanometers to 500 nanometers.

3. The preparation method according to claim 1, characterized in that, In step S3, the physical vapor deposition process is magnetron sputtering, and the key parameter is sputtering gas pressure. During magnetron sputtering, the intrinsic stress of the metal functional thin film layer is continuously controlled to change between compressive stress and tensile stress by adjusting the sputtering gas pressure. The intrinsic stress ranges from -1 to 1 gigapascal, and the sputtering gas pressure ranges from 0.1 pascal to 5 pascal.

4. The preparation method according to claim 3, characterized in that, In step S3, there exists a critical pressure; when the sputtering pressure is lower than the critical pressure, the functional thin film layer forms compressive stress; when the sputtering pressure is higher than the critical pressure, tensile stress is formed; when the sputtering pressure reaches the critical pressure, neutral stress is formed; the critical pressure ranges from 0.4 to 4 Pascals; the neutral pressure ranges from -20 to 20 MPa.

5. The preparation method according to claim 1, characterized in that, In step S3, the process parameters for magnetron sputtering also include: a vacuum level of 5 × 10⁻⁶. -4 Below Pascal, the purity of the metal target is above 99.99%, the substrate temperature is between 10-60℃, and the sputtering rate is 10-500 nm / min.

6. The preparation method according to claim 1, characterized in that, In step S5, the device contour is separated by laser, chemical or plasma etching methods to achieve the separation of the first flexible packaging layer from the rigid temporary substrate.

7. A self-forming flexible bioelectronic device prepared by the method according to any one of claims 1-6, characterized in that, It includes a first flexible encapsulation layer, a functional thin film layer with a preset pattern, and a second flexible encapsulation layer stacked in sequence; the functional thin film layer has a preset intrinsic stress, which enables the composite film system composed of the first flexible encapsulation layer, the functional thin film layer and the second flexible encapsulation layer to spontaneously maintain a stable three-dimensional configuration when the device is in a self-supporting state.

8. The self-forming flexible bioelectronic device according to claim 7, characterized in that, By designing the pattern of the functional thin film layer and pre-setting the spatial distribution of intrinsic stress, the device can be selected from one or a combination of the following forms: (a) Self-curling probe: The functional thin film layer is a uniform compressive stress layer, which causes the device to curl into a tubular or needle-like structure; (b) Self-encapsulating probe: The functional thin film layer is a uniform tensile stress layer, which makes the device curl into a sleeve structure that can encapsulate biological tissue; (c) Conformal planar array: The functional thin film layer is a near-neutral stress layer, which enables the device to maintain a planar flexible structure that can conform to the curved surface of biological tissue.

9. An application of the self-forming flexible bioelectronic device according to claim 7 or 8 as a neural interface, characterized in that, The neural interface includes a deep brain probe, a cortical electrode array, or a peripheral nerve cuff electrode.

10. A neural interface system, characterized in that, It includes a self-forming flexible bioelectronic device as described in claim 7 or 8, and a signal processing unit electrically connected to the circuit pattern of said device.

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