Polymer encapsulation system-based optical genetic probe integrated with tower loose type flexible optical waveguide

Abstract

The invention discloses a polymer encapsulation system-based tamponade type flexible optical waveguide integrated optical genetic probe, the appearance of an implantation part of the probe is of a flat tamponade structure, and the probe comprises a cuboid trunk and a crown which is positioned at the tail end of the trunk and is formed by nesting and stacking at least two layers of prisms with tips; the internal structure of the optical genetic probe comprises a polymer cladding and a waveguide core layer; the waveguide core layer is located inside the polymer cladding or above the polymer cladding; the refractive index of the waveguide core layer is greater than that of the polymer cladding layer. The tower-loose structure of the probe can disperse the tip stress of the probe during implantation, protect the functional units distributed at the extension part of a tree crown, and prevent the layering of the probe structure from causing the peeling, damage and failure of the functional units; after implantation, tooth-shaped anchoring is formed between the extending part of the tree crown and the brain tissue, stronger interaction is generated, probe displacement caused by micro-motion in the brain tissue is effectively resisted, and the stability of long-term signal acquisition sites is ensured.

Description

Technical Field

[0001] This invention relates to the field of micro-nano photonics device design, specifically to an optogenetic probe integrated with a polymer-encapsulated Tassun-type flexible optical waveguide. Background Technology

[0002] Waveguide-integrated optogenetic probes are important tools for neuromodulation research. Their flexible design can reduce tissue damage and extend the theoretical lifespan of the probes. However, the actual lifespan of flexible probes is still limited by neural interface failure caused by micro-movements in brain tissue. Compared to rigid probes, the Young's modulus of flexible probes is closer to that of brain tissue, but it is still not a perfect match. Therefore, micro-movements in brain tissue (originating from physiological movements such as breathing and heartbeat; behavioral movements of organisms; vibrations of external devices) still cause continuous friction between the probe and brain tissue, triggering chronic inflammatory responses and glial scarring. This also causes probe drift, resulting in the distance between the electrode and the target neuron exceeding the effective recording range (>100 μm), leading to signal attenuation or even loss of the target signal. To improve stability, current strategies for anchoring flexible probes to brain tissue are mainly divided into structural fusion and interfacial adhesion. The structural fusion strategy (nanomesh / tassel-type self-assembled probes) increases the specific surface area between the probe and brain tissue, thereby enhancing probe anchoring, i.e., the interaction between the probe and brain tissue. However, their excessive softness makes implantation difficult, often requiring rigid guiding devices or mechanically reinforcing coatings. The subsequent removal of rigid guiding devices demands a high level of surgical skill, while mechanically reinforcing coatings introduce additional preparation steps and necessitate waiting for complete coating degradation before experiments can proceed. Interfacial adhesion methods (such as protein coatings) face challenges related to coating peeling during implantation and signal interference from post-implantation degradation in vivo.

[0003] Furthermore, during implantation, the probe must also address the issues of interlayer delamination and electrode detachment caused by high stress concentration. Existing solutions primarily rely on additional coatings to transfer stress or reduce friction between the probe and brain tissue. However, these coatings must simultaneously address the problems of interfacial failure and biochemical interference caused by coating peeling during implantation and long-term degradation in vivo. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention proposes an optogenetic probe integrated with a polymer-encapsulated, pine-shaped flexible optical waveguide. This structure incorporates a pine-shaped geometry into traditional probe design, arranging functional units within the extended portion of the pine-shaped canopy. The pine-shaped canopy disperses stress at the probe tip during implantation, protecting the functional units. After implantation, the multi-layered canopy extensions form a serrated anchor with brain tissue, resisting displacement caused by intracranial micro-movements and ensuring long-term effective operation of the probe.

[0005] The objective of this invention is achieved through the following technical solution:

[0006] An optogenetic probe based on a polymer-encapsulated flexible optical waveguide integrated with a pine-shaped structure, wherein the implanted part of the optogenetic probe has a flat pine-shaped structure, including a cuboid trunk and a crown at the end of the trunk formed by nested stacking of no less than two layers of pointed prisms;

[0007] The internal structure of the optogenetic probe includes a polymer cladding and a waveguide core.

[0008] The waveguide core layer is located inside the polymer cladding or above the polymer cladding;

[0009] The refractive index of the waveguide core is greater than that of the polymer cladding.

[0010] Furthermore, the width of each layer of the canopy extending outward from one side of the trunk is not less than 20 μm; the ratio of the width of each layer of the canopy to the width of the trunk is not greater than 5; and the angle of the tips extending outward from both sides of each layer of the canopy is in the range of 40°-70°.

[0011] Furthermore, to prevent the sharp tips on both sides of the canopy from piercing the object to be detected and to increase the contact area with the object, the ends on both sides of each layer of the canopy can be selectively formed into cylindrical structures.

[0012] Furthermore, the polymer cladding material must meet biocompatibility requirements, preferably any one of SU-8, colorless polyimide (PI), Parylene C, polymethyl methacrylate (PMMA), Epoclad, and polydimethylsiloxane (PDMS). Furthermore, the waveguide core material must also meet biocompatibility requirements, preferably any one of silicon nitride, titanium dioxide, Epocore, SU-8, and polycarbonate; other suitable materials such as zinc oxide and alumina are also applicable.

[0013] Furthermore, when the waveguide core layer is an inorganic material, the thickness of a single waveguide is 50 nm-1 μm and the width is 150 nm-2 μm; when the waveguide core layer is an organic material, the thickness of a single waveguide is 0.5 μm-30 μm and the width is 1 μm-300 μm. The waveguide light-emitting unit is preferably located in the canopy extension area.

[0014] Furthermore, the internal structure of the optogenetic probe also includes an electrode interlayer composed of multiple electrodes, the electrode interlayer and the waveguide core layer are both located inside the polymer cladding and separated from each other; the electrodes are exposed at the recording site to contact the object to be detected; the exposed electrode area, i.e. the electrical recording unit, is preferentially located in the canopy extension area.

[0015] Furthermore, the electrode material is selected from any one of the six single metals: platinum, gold, tungsten, iridium, aluminum, and copper; or from an alloy of metal materials, such as aluminum-copper or platinum-iridium; or from a conductive metal compound material, such as titanium nitride, zinc oxide, indium tin oxide, or iridium oxide; or from any one of the five non-metallic materials: poly(3,4-ethylenedioxythiophene):poly(styrene sulfonic acid) (PEDOT:PSS), polyaniline, graphene, MXenes, and carbon nanotubes; or from any two or more of the above single metals, metal alloys, metal compounds, and non-metallic materials mixed in any proportion.

[0016] The beneficial effects of this invention are as follows:

[0017] (1) When the probe of the present invention is implanted, the tower-shaped structure can disperse the stress concentrated at the tip of the probe during the implantation stage, protect the functional units including the light emitting unit, and avoid probe structure delamination and damage and failure of functional units, thus ensuring the normal operation of the probe.

[0018] (2) After implantation, the multi-layered tip structure of the probe of the present invention forms a tooth-like anchor with the brain tissue, generating a stronger interaction. This can reduce the inflammatory response of the tissue because the distributed anchoring greatly reduces the shear stress at the probe-tissue interface, effectively inhibiting glial cell activation and neuronal apoptosis, and reducing glial scar formation. It can also maintain long-term signal coupling because the probe moves synchronously with the brain tissue, ensuring that the distance between the recording site and the target neuron is stable within the effective range of cellular electrical signal acquisition. This ensures that the probe serves the target neuron population for a long time and stably, achieving the accuracy and long-term reliability of the signal acquisition site.

[0019] (3) This invention starts from the probe itself, only changes the two-dimensional geometric configuration, and does not introduce additional process steps or complex operations. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the optogenetic probe integrated into the Tassun-type flexible optical waveguide based on the polymer encapsulation system of the present invention.

[0021] Figure 2 The figures show planar diagrams of different geometric configurations of the Tower Pine probe structure. In Figure (a), the traditional Tower Pine structure is shown. In Figure (b), the extended Tower Pine structure 1 is shown. In Figure (c), the extended Tower Pine structure 2 is shown. In Figure (d) to (g), the irregular Tower Pine structures 1 to 4 are shown respectively. In Figure (h), the fractal Tower Pine structure is shown.

[0022] Figure 3The image shows a top view of a traditional pine-shaped waveguide probe structure with a colorless PI cladding, a titanium dioxide core layer, and a gold electrode interlayer, as well as a cross-sectional view of the probe in the trunk section. The light emission unit and the electrical recording unit are mainly distributed at the canopy extension of the pine-shaped structure.

[0023] Figure 4 The image shows a top view of the SU-8 cladding and silicon nitride core layer irregular tower-pine waveguide probe structure and a cross-sectional view of the probe in the trunk section, where the light emitting units are distributed at the canopy extension of the tower-pine structure.

[0024] Figure 5 The image shows a top view of a fractal tower-pine waveguide probe structure with PMMA cladding, SU-8 core, and PEDOT:PSS electrode interlayer, as well as a cross-sectional view of the probe in the trunk section, where the light emitting unit and the electrical recording unit are distributed at the canopy extension of the tower-pine structure. Detailed Implementation

[0025] The present invention will be described in detail below with reference to preferred embodiments, and the purpose and effects of the present invention will become clearer. It should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0026] The proposed optogenetic probe, based on a polymer-encapsulated flexible optical waveguide, incorporates a pine-like geometry into traditional probe design. Utilizing its multi-layered canopy characteristics, the probe disperses stress during implantation through the extended multi-layered tips, reducing the risk of damage to the light-emitting and recording units located at the canopy extensions. After implantation, the canopy's tooth-like engagement with brain tissue enhances anchoring stability, resisting micro-movement displacement and ensuring long-term effective operation.

[0027] like Figure 1 As shown, the implantation portion of the optogenetic probe has a flattened, pyramidal structure, comprising a cuboid trunk and a crown at the end of the trunk formed by nested stacks of at least two layers of pointed prisms. Specifically, the crown extends outwards with serrations in the width direction relative to the trunk, and has multiple layers of stacked serrations along its length. The end of the entire crown forms the tip for probe implantation, thus creating a flattened, pyramidal structure similar to that of a pine tree.

[0028] like Figure 2 As shown, the tree crown has no fixed shape, including traditional tower pine structure, extended tower pine structure, irregular tower pine structure, and more fractal tower pine structures. For example... Figure 2 As shown in (a), the traditional tower pine structure consists of stacked canopies with straight edges, each canopy layer considered as an identical isosceles triangle. Besides the traditional structure, other structures can originate from the arrangement requirements of the electrical recording and light emission channels or certain mechanical design requirements. Adjusting the shape of each canopy layer to be the same arrowhead or rhombus shape can form an extended tower pine structure, such as... Figure 2 (b) and (c) in the text. Introducing a curved crown edge into the traditional structure can be categorized as an irregular tower pine structure, such as... Figure 2 (d) and (e) in the text. Asymmetrical tower structures designed for specific mechanical requirements can also be classified as irregular tower structures, such as... Figure 2 (f) in the text. Furthermore, those whose basic characteristics are not entirely the same across each canopy layer can also be classified as heteromorphic tower pines, such as... Figure 2 (g) In the fractal tower pine structure, substructures are generated at the tips of the conventional / extended / irregular crowns in the width direction. These substructures can be similar to or different from the main crown structure. For example, to prevent the tips on both sides of the crown's width from piercing brain tissue and to increase the contact area with brain tissue, the tips on both sides of the crown's width are modified into cylindrical structures, such as... Figure 2 (h) in the middle.

[0029] These diverse tower pine structures can be simplified into traditional tower pine structures and meet the design requirements of traditional tower pine structures.

[0030] The above discussion concerns the external shape of the probe. The internal structure of the optogenetic probe includes a polymer cladding and a waveguide core, with the waveguide core located inside or above the polymer cladding; the refractive index of the waveguide core is greater than that of the polymer cladding.

[0031] Based on this, the key geometric parameters of the canopy are designed as follows: the width of each layer extending to one side of the trunk is not less than 20 μm to accommodate the electrical recording and light emission units; the ratio of the width of each layer to the width of the trunk is not greater than 5, that is, the ratio of the width of the extension to the width of the trunk is not greater than 2:1; the angle range of the tips extending to both sides of each layer is 40°-70°. The number of canopy layers is set according to the depth of the target brain region (usually 2-10 layers). Increasing the number of layers can enhance the anchoring effect, especially suitable for implantation of long probes (>5 mm) in deep brain regions (such as the hippocampus and hypothalamus), but the relationship between the number of layers and implantation trauma needs to be balanced.

[0032] The materials for optogenetic probes are discussed below. The polymer cladding material must meet the requirements of biocompatibility and a refractive index lower than that of the waveguide core layer. Suitable materials include SU-8, colorless PI, Parylene C, PMMA, Epoclad, and PDMS. The waveguide core layer material must meet the requirements of biocompatibility and a refractive index greater than that of the cladding. Suitable materials include silicon nitride, titanium dioxide, Epocore, SU-8, and polycarbonate. Other suitable materials, such as zinc oxide, are also applicable.

[0033] When inorganic materials are used for the waveguide core layer, the thickness of a single waveguide is 50nm-1μm and the width is 150nm-2μm; when organic materials are used for the waveguide core layer, the thickness of a single waveguide is 0.5μm-30μm and the width is 1μm-300μm.

[0034] like Figure 1 As shown, the portion of the waveguide core layer located on the rigid substrate can be used to design a light-guiding network, serving multiple light-emitting sites or directions. However, the area designed with the light network is not used as the implantation part of the probe; the implantation part has a cross-section of only one or more rectangular waveguides. The waveguide light-emitting points are preferably located in the canopy extension area, but can also be arranged according to the needs of photogenetic sites.

[0035] The electrode interlayer in the probe structure is an optional design. The electrode interlayer is recommended in the following scenarios: when verifying the causal relationship between light stimulation and target neuron activity (e.g., neural circuit mechanism analysis), the integrated electrodes can achieve synchronous electrical signal recording with spatial precision at the stimulation site, avoiding positioning errors caused by multiple implantations and immune responses triggered by secondary surgery; when long-term stable acquisition of stimulus-response correlation data is required, the integrated electrodes eliminate mechanical displacement deviations of independent probes (caused by brain tissue pulsation), maintaining signal stability; when constructing a real-time closed-loop light modulation system, the integrated electrodes provide millisecond-level neural feedback to drive dynamic adjustment of light parameters.

[0036] Electrode interlayer materials must possess conductivity, biocompatibility, and corrosion resistance, including metallic materials (platinum / gold / tungsten / iridium / aluminum / copper), alloy materials (aluminum-copper), and metal compound materials (titanium nitride, zinc oxide, iridium oxide), or non-metallic materials (PEDOT:PSS / polyaniline / graphene / MXenes / carbon nanotubes). Any two or more of single metals, metal alloys, metal compounds, and non-metallic materials can be mixed in any proportion.

[0037] A polymer material of approximately 2 μm thickness is required to separate the electrode interlayer from the waveguide core. At the recording site, one side of the electrode interlayer is uncovered and in direct contact with the neuron or cerebrospinal fluid; this exposed site is preferably located in the canopy extension region.

[0038] Several specific implementation examples are given below.

[0039] Example 1

[0040] The traditional pine needle probe uses colorless PI as the cladding, titanium dioxide as the waveguide core, and gold as the electrode interlayer. The canopy has a two-layer structure, each layer extending 40 μm on one side, with a canopy width:trunk width ratio of 1.67:1 and a tip extension angle of 40°. Four waveguide light-emitting units (120 nm thick × 200 nm wide) and eight electrical recording units are distributed in the canopy extension area, with one electrode recording point located at the probe tip. A top view of the probe structure and a cross-sectional view of the probe in the trunk section are shown below. Figure 3 As shown.

[0041] Example 2

[0042] The irregularly shaped tower-like probe uses Parylene C as the cladding and silicon nitride as the waveguide core. The canopy has a five-layer structure: along the direction from the canopy to the trunk, the first layer near the end of the canopy extends 40 μm wide on one side with a tip angle of 45°; the second to fifth layers extend 30 μm wide with a tip angle of 50°. Based on the first layer, the canopy width to trunk width ratio is 2:1. Five waveguide light-emitting units (200 nm thick × 400 nm wide) are distributed in the canopy extension area. A top view of the probe structure and a cross-sectional view of the probe on the trunk are shown below. Figure 4 As shown.

[0043] Example 3

[0044] The fractal tower-type probe uses PMMA as the cladding, SU-8 as the waveguide core, and PEDOT:PSS as the electrode interlayer. The canopy has an 8-layer structure: along the direction from the canopy to the trunk, the first layer near the canopy tip extends 50 μm wide on one side with a 50° tip angle; the second to eighth layers extend 35 μm wide with a 40° tip angle. Based on the first layer, the canopy width:trunk width = 1.7:1. The canopy tip is modified into a 3 μm radius cylindrical structure. Four waveguide light-emitting units (2 μm thick × 5 μm wide) and 12 electrical recording units are distributed in the canopy extension area. A top view of the probe structure and a cross-sectional view of the trunk are shown below. Figure 5 As shown.

[0045] It will be understood by those skilled in the art that the above descriptions are merely preferred examples of the invention and are not intended to limit the invention. Although the invention has been described in detail with reference to the foregoing examples, those skilled in the art can still modify the technical solutions described in the foregoing examples or make equivalent substitutions for some of the technical features. All modifications and equivalent substitutions made within the spirit and principles of the invention should be included within the scope of protection of the invention.

Claims

1. An optogenetic probe integrated with a polymer-encapsulated, flexible optical waveguide, characterized in that, The implantation part of the optogenetic probe has a flat, pyramidal structure, including a rectangular trunk and a crown at the end of the trunk formed by nested stacks of at least two layers of pointed prisms. The internal structure of the optogenetic probe includes a polymer cladding and a waveguide core. The waveguide core layer is located inside the polymer cladding or above the polymer cladding; The refractive index of the waveguide core is greater than that of the polymer cladding.

2. The probe according to claim 1, characterized in that: Each layer of the canopy extends at least 20 μm over one side of the trunk; The ratio of the width of each layer of the canopy to the width of the trunk is no greater than 5; The angle of the tips extending from both sides of each layer of the canopy ranges from 40° to 70°.

3. The optogenetic probe integrated with a polymer-encapsulated flexible optical waveguide according to claim 1, characterized in that, To prevent the sharp tips on both sides of the canopy from piercing the object to be detected and to increase the contact area with the object, the ends of both sides of the width of each layer of the canopy are formed into a cylindrical structure.

4. The optogenetic probe integrated with a polymer-encapsulated flexible optical waveguide according to claim 1, characterized in that, The materials of the polymer cladding and waveguide core must be biocompatible.

5. The optogenetic probe integrated with a polymer-encapsulated flexible optical waveguide according to claim 4, characterized in that, The polymer cladding material is selected from any one of SU-8, colorless polyimide, Parylene C, polymethyl methacrylate, Epoclad, and polydimethylsiloxane.

6. The optogenetic probe integrated with a polymer-encapsulated flexible optical waveguide according to claim 4, characterized in that, The waveguide core layer is made of any one of silicon nitride, titanium dioxide, Epocore, SU-8, or polycarbonate.

7. The optogenetic probe integrated with a polymer-encapsulated flexible optical waveguide according to claim 6, characterized in that: When the waveguide core layer is an inorganic material, the thickness of a single waveguide is 50nm-1μm and the width is 150nm-2μm; when the waveguide core layer is an organic material, the thickness of a single waveguide is 0.5μm-30μm and the width is 1μm-300μm. The light-emitting part of the waveguide, that is, the area where the light-emitting units are arranged, is where the tree canopy extends.

8. The optogenetic probe integrated with a polymer-encapsulated flexible optical waveguide according to claim 1, characterized in that: The internal structure of the optogenetic probe also includes an electrode sandwich composed of multiple electrodes, and the electrode sandwich and the waveguide core are both located inside the polymer cladding and separated from each other. The electrode is exposed at the recording site to contact the object to be detected; The exposed electrode area is the region where the electrical recording units are arranged in the canopy.

9. The optogenetic probe integrated with a polymer-encapsulated flexible optical waveguide according to claim 8, characterized in that, The electrode material is selected from any one of the six single metals: platinum, gold, tungsten, iridium, aluminum, and copper. or, Any one of aluminum-copper alloy and platinum-iridium alloy; or, Any one of the four metal compounds: titanium nitride, zinc oxide, indium tin oxide, and iridium oxide; or, Selected from any one of the following five non-metallic materials: poly(3,4-ethylenedioxythiophene), poly(styrene sulfonic acid), polyaniline, graphene, MXenes, and carbon nanotubes; or, It can be used by mixing any two or more of the above six single metals, two metal alloys, four metal compounds, and five non-metallic materials in any proportion.

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