Devices and methods relating to high density bioelectronic fibers

Abstract

In certain examples, methods and devices (e.g., semiconductor structures) involve the use of a 1D fiber material that is characterized by a fiber structure having one or more deformations selected from the group consisting of spirals, curls, and wrinkles. Such devices may include one or more wire contact regions adjacent and unconnected to the 1D fiber material for contacting the 1D fiber material, and may include sensor circuitry (integrated with the 1D fiber material) to sense parameters in response to at least one of the following variations: pressure, capacitance, and strain. In more specific examples, such devices include a polymer-based substrate having one or more characteristics selected from the group consisting of: self-adhesion, stretchability; and the elasticity of the original shape can be recovered after stretching.

Description

Background Technology

[0001] The aspects of this disclosure generally relate to the field of sensor-related circuits and materials, and can be exemplified by their use in applications including biomedical devices.

[0002] Using electronic fibers as an example of a technology relevant to this disclosure, for ease of discussion, it is understood that electronic fibers have attracted considerable attention due to their miniaturized structure, significant deformability, and applications in a variety of functions such as sensing, actuation, tissue regulation, energy harvesting, and luminescence. Despite their potential advantages, the fabrication of electronic fibers remains a challenge because they are incompatible with conventional microfabrication techniques originally developed for planar substrates. Consequently, currently available fiber devices suffer from low density, limited functionality, and inaccurate component positioning. Therefore, integrating microfabrication techniques with fiber production holds immense potential and opens up new possibilities in various fields, including implantable biomedical devices, electronic textiles, and wearable devices.

[0003] In the specific context of biological applications, bioelectronic fibers show promise in applications (e.g., research and / or clinical) due to their compactness, ease of implantation, and ability to integrate advanced functions such as sensing, recording, and stimulation. However, previously known such devices are disadvantaged due to one or more reasons such as large volume, rigidity, low functionality, and low density of active components. These limitations stem from the difficulty in integrating multiple components onto 1D fiber devices because the thin, curved, and extended structures of 1D fiber devices are incompatible with conventional microfabrication methods (e.g., photolithography).

[0004] In specific contexts, biomedical devices with 1D geometry, such as surgical sutures, biopsy needles, endoscopes, guidewires, pressure probes, fiberscopes, and deep brain stimulation electrodes, have been widely used clinically for decades. Compared to 3D systems and 2D films, 1D devices are more compact and can adapt to complex deformations. Therefore, 1D devices are advantageous for deep implantation into tissues and body cavities via minimally invasive procedures. Furthermore, they can be easily removed after their sensing or therapeutic functions are completed. Among various examples of 1D devices, electronic fibers have received considerable attention. With recent advances in materials, manufacturing, optics, and electronics, electronic fibers have acquired new functions, including sensing, actuation, tissue modulation, energy harvesting, and luminescence. Despite their potential advantages, the fabrication of electronic fibers remains a challenge because they are incompatible with conventional microfabrication techniques originally developed for planar substrates. Therefore, currently available fiber devices suffer from low density, limited functionality, and inaccurate component positioning. To date, methods such as fiber spinning, 3D printing, (micro)fluidics, functionalization / coating of commercial fibers, and thermal stretching have been used to fabricate 1D fiber devices. While electronic fibers prepared by thermal stretching can support dozens of channels (e.g., for signal transmission) and multiple functional components, the active regions (e.g., sensing regions) are typically located at the fiber's tip, i.e., without longitudinal distribution. Furthermore, obtaining high-density fibers with precise control over the device's structure, position, and orientation remains challenging. Recently, examples of on-fiber lithography have been introduced to break the longitudinal symmetry of fibers and introduce micropatterned components. However, this process remains time-consuming, imprecise, and challenging for high-throughput production. In addition to the aforementioned limitations, compatibility requirements with thermal stretching processes significantly reduce the range of materials that can be used.

[0005] Overview of aspects and examples

[0006] The various examples / implementations presented in this disclosure address problems such as those described above and / or other problems that may become clear from the following disclosure. For example, some of these disclosed aspects relate to methods and apparatus for using or utilizing fiber-based devices, and methods for using and manufacturing fiber-based devices.

[0007] In specific examples, this disclosure relates to apparatus (e.g., semiconductor structures) and / or (use and manufacture) methods, wherein the apparatus or method relates to 1D fibrous materials characterized by having a fibrous structure having one or more deformations selected from: helical, crimped, and pleated. For example, the method according to this disclosure may relate to the use of an apparatus, or the manufacture of said apparatus, which corresponds to or includes a 1D fibrous material characterized by having a fibrous structure having one or more of these deformations.

[0008] In a more specific aspect of this disclosure, the device with the above-described features is integrated with a semiconductor structure, and the device may include one or more line contact regions adjacent to but not connected to the 1D fiber material for contacting the 1D fiber material, and / or may include sensor circuitry (integrated with the 1D fiber material) to sense parameters in response to at least one of the following changes: pressure, capacitance, and strain. In a more specific example, such a device includes a polymer-based substrate having one or more properties selected from: self-adhesion, stretchability; and elasticity that allows it to recover its original shape after stretching.

[0009] In other exemplary contexts, methods of manufacturing such electronic fibers involve customizing (or optimizing for a particular application) one or more parameters relating to the electronic fibers in accordance with this disclosure to achieve precise control over the structure, dimensions and / or composition of the fibers developed therein, and / or one or more manufacturing aspects for automating the fiber preparation process.

[0010] In more specific examples related to the methods and / or devices described above, exemplary aspects include a manufacturing method for transforming 2D films containing relevant microfabrication devices into 1D fibers based on helical deformation. This method allows for the creation of high-density, multifunctional bioelectronic fibers while enabling precise control over their longitudinal, angular, and radial positioning (e.g., for motion mapping, serotonin sensing, and tissue stimulation in dynamically flexible gastrointestinal (GI) systems, as successfully demonstrated and disclosed herein, and for single-neuron recording in the brain). In related examples, post-fabricated bioelectronic fibers demonstrate significant potential for next-generation clinical monitoring and modulation applications, particularly for minimally invasive deployment in the GI tract and other curved and confined areas of the body.

[0011] In the context of biological and other specific application fibers, another concrete example aspect of this disclosure is a method for preparing high-density soft electronic fibers capable of carrying a variety of functional components. In such more specific methods, fabrication can be performed on a 2D substrate, which is then rolled into a 1D structure.

[0012] According to one exemplary embodiment, this disclosure relates to a method comprising the steps of: providing a 1D fibrous material as a fibrous structure having one or more deformations selected from helical, coiled, or pleated forms, wherein the 1D fibrous material is configured to transmit signals indicative of one or more biomedical functions. In a more specific embodiment, the 1D fibrous material is integrated with circuitry including at least one microfabrication component and / or device to transmit signals indicative of biomedical functions. The biomedical functions may be selected from: monitoring physiological parameters or responses in a living organism; and introducing or inducing biomodulation in a curved or confined region of a living organism. Furthermore, in such more specific embodiments, the 1D fibrous material can be used to simultaneously achieve: real-time mapping of biomedical signals obtained from a living organism via the 1D fibrous material, and stimulation of tissues in a living organism, wherein the circuitry facilitates both the real-time mapping and the tissue stimulation.

[0013] According to various other exemplary embodiments, this disclosure is implemented through such deformation processing methods (e.g., involving deformation by winding, spiraling, etc.) and used to create and / or modify various 1D devices, some of which include 1D devices as part of: biomedical applications (e.g., implantable probes, electrodes, leads, catheters, guidewires, fiberscopes, endoscopes, biopsy needles, and / or sutures); fibers for electronic textiles and wearable devices, fiber electrical connectors, fiber actuators (e.g., artificial muscles for robots); and various general-purpose sensing applications. In addition to providing electronic functionality, examples of such deformation processing methods disclosed can also be used to create fibers with optical and optoelectronic functions.

[0014] The foregoing discussion is not intended to describe every aspect, implementation, or embodiment of this disclosure. Various embodiments are also illustrated in the following figures and detailed descriptions.

[0015] Brief description of the attached figures

[0016] A more complete understanding of the various exemplary embodiments (including experimental embodiments) can be obtained by considering the accompanying drawings and the following detailed description, each in accordance with this disclosure, wherein: Figure 1A-1H This is a set of schematic diagrams illustrating certain exemplary aspects of this disclosure, wherein: Figure 1A This is an illustrative description of an exemplary method for 2D thin film deformation. Figure 1B and Figure 1C These are photographs of such thin films (including thin films with some sensing components, see sections i and ii). Figure 1D These are microscopic images of high-density deformable bio-electronic fibers (t-BEF). Figure 1E , 1F1G and 1H are respectively a bioelectronic fiber (1E), a schematic illustration of the film size and deformation process (1F), and a diagram showing the parameters (1G) and properties (1H) of an example fiber. Figures 2A-2F This is a set of schematic diagrams illustrating certain exemplary aspects of this disclosure, wherein: Figure 2A and 2B These are schematic illustrations showing the first and second portions of an exemplary deformation process (including the forces involved in the process). Figure 2C These are a set of microscope images showing the winding process under different conditions. Figure 2D It is a set of 2D exemplary layout designs and corresponding fibers. Figure 2E These are images showing advanced features that can be integrated into such fibers. Figure 2F This is an illustration showing another example aspect of an exemplary deformation process according to this disclosure; Figure 3A-3L This is a set of diagrams illustrating certain exemplary aspects: Figures 3A-3B This demonstrates the deployment of t-BEF into the small intestine of pigs. Figure 3C It is a record of the natural movement of the small intestine. Figure 3D This is a 2D design schematic of a bifunctional t-BEF. Figure 3E From Figure 3D The image shows a t-BEF obtained from the 2D design shown. Figure 3F The output of the pressure sensor in response to different stimuli is shown. Figure 3G It is the sum of the maximum responses obtained under different voltage stimuli. Figure 3H This is a schematic diagram showing the use of distributed stimulation electrodes. Figure 3I It is a demonstration of a closed-loop feedback system for programmable stimuli. Figure 3J This is a diagram illustrating the use of SSRI injection. Figure 3K The chart shows drug-induced changes in intraluminal serotonin concentration. Figure 3L The graph shows the electrochemical sensing of SSRI-induced serotonin. Figure 4A-4L This is a set of schematic diagrams illustrating exemplary aspects of this disclosure, wherein: Figure 4A This is a schematic diagram of the design of a 2D thin film used to prepare neural t-BEFs. Figure 4B It is an image showing the nerve t-BEF tip with a recording PEDOT microelectrode. Figure 4C The impedance measurements collected from microelectrodes on 60 fibers are shown in the distribution. Figure 4D This is a schematic diagram showing the setup for recording neural signals in a conscious mouse. Figure 4E The data is the raw data obtained from the four recording electrodes. Figure 4F It is an overlay map of hundreds of spikes collected via neural t-BEF. Figure 4G There are four related graphs. Figure 4H It is an ISI violation. Figure 4I-4J It is a sharp wave ripple (SWR) detected in the hippocampus. Figure 4K -L is a spectrum diagram showing a typical increase in power; Figures 5A-5F This is a set of schematic diagrams illustrating certain exemplary aspects of this disclosure, wherein Figure 5A and 5B It is a schematic illustration showing two parts of the deformation process. Figure 5C The display shows how adjusting different parameters optimizes the winding process. Figure 5D The image depicts the tight interlayer adhesion after film deformation using thermal annealing. Figure 5E It is an image of eccentrically wound fibers, showing densely packed layers. Figure 5F This is a cross-sectional image of the fiber, showing well-bonded layers; and Figures 6A-6H This is a set of images and diagrams illustrating certain exemplary aspects of this disclosure relating to high-density electrical recording fibers, wherein: Figure 6A It is a photo of a 2D thin film. Figure 6B yes Figure 6A Images of the exposed areas of the thin film. Figures 6C-6D These are related microscope images (showing the 230 µm fiber obtained after winding). Figure 6E It displays cross-sectional images of fibers with different winding layers. Figure 6F-6G It is a 320-channel SEM image of the fiber. Figure 6H It is a graph displaying impedance analysis.

[0017] While modifications and alternatives may be made to the various embodiments described herein, aspects thereof have been shown by way of example in the accompanying drawings and will be described in detail. However, it should be understood that this disclosure is not intended to limit it to the specific embodiments described. Rather, it is intended to cover all modifications, equivalents, and alternatives falling within the scope of this disclosure, including aspects defined in the claims. Furthermore, the term "example" as used throughout this application is for illustrative purposes only and not for limitation. Detailed Implementation

[0018] The aspects of this disclosure are intended to be applicable to a wide variety of apparatuses, systems, and methods relating to fiber-based devices and methods of using and manufacturing fiber-based devices (e.g., including but not limited to structural aspects of partially manufactured and / or assembled such devices) and devices characterized (at least in part) by specific materials and integrated circuits for a particular application. While this disclosure is not necessarily limited to such aspects and examples, the discussion in a particular context or application can be understood from the specific examples in the following description.

[0019] In certain exemplary embodiments and specific aspects, this disclosure relates to apparatuses and / or methods for providing (i.e., in use, testing, and / or manufacturing) 1D fibrous materials, wherein said apparatus or method relates to 1D fibrous materials characterized by having a fibrous structure having one or more deformations selected from: helical, crimped, and pleated. For example, such methods may involve testing apparatus manufactured according to the apparatus and / or methods of this disclosure, said apparatus corresponding to or including 1D fibrous materials characterized by having a fibrous structure having one or more of these deformations.

[0020] In the context of biological and other specific application fibers, another specific example aspect of this disclosure is a method for fabricating high-density soft electronic fibers capable of carrying various functional components. In such a specific method, the fabrication of such fibers is performed on a 2D substrate, which is then wound into a 1D structure. Thus, the 1D fiber material is provided as a fiber structure having one or more deformations selected from helices, coils, or pleats, and the 1D fiber material is configured to transmit signals indicating one or more biomedical functions. In a more specific embodiment, the 1D fiber material is integrated with circuitry including at least one microfabrication component and / or device to transmit signals indicating biomedical functions. The biomedical functions may be selected from: monitoring physiological parameters or responses in a living organism; and introducing or inducing biomodulation in a curved or confined region of the living organism. Furthermore, in such more specific embodiments, the 1D fiber material can be used to simultaneously achieve: real-time mapping of biomedical signals obtained from a living organism via the 1D fiber material, and stimulation of tissues in a living organism, wherein the circuitry facilitates both the real-time mapping and the tissue stimulation.

[0021] In this disclosure, various specific details are set forth to describe the specific examples presented herein. However, it will be apparent to those skilled in the art that one or more other examples and / or variations thereof may be practiced without following all the specific details set forth below. In other instances, well-known features have not been described in detail so as not to obscure the description of the examples herein. For ease of illustration, the same connotations and / or reference numerals may be used in different figures to refer to the same elements or additional instances of the same elements. Furthermore, although in some instances aspects and features may be described in separate figures, it should be understood that features from one figure or embodiment may be combined with features from another figure or embodiment, even if such combination is not explicitly shown or described as a combination. Consistent with the foregoing, apparatus or methods of manufacture of this kind may relate to and claim priority in U.S. Provisional Application Serial No. 63 / 528,846 (STFD.458P1S23-326), filed July 25, 2023, and its Appendix AD. To the extent permitted, such topics are included in the references in their entirety, including those further aspects and examples (such as experimental and / or more detailed implementations) that may be useful for supplementation and / or clarification.

[0022] Several significant advances have been achieved through this experimental work, including, for example, the following: First, a method has been implemented to create high-density electronic fibers while still utilizing conventional microfabrication techniques. This method allows for the transformation of materials, devices, circuits, and manufacturing processes from mature conventional planar systems to thin, flexible, and extended 1D fibers. Second, this experimental work demonstrates the ability to map GI signals in real time and simultaneously stimulate tissues, while minimizing interference with the natural movement of the body and organs. Furthermore, this experimental work enables high-density single-neuron recording using elastomer-based fibers, providing a new level of flexibility unattainable by previous single-neuron recording microelectrode arrays.

[0023] As described above, certain exemplary aspects of this disclosure relate to methods and structures for transforming 1D fibers from 2D structures. Depending on the specific process used and / or the materials selected, in various examples, the fiber core can be implemented as an optical fiber, a hollow fiber, or a solid material that can be removed by solvent or vapor etching to form a hollow structure (see, for example...). Figure 1E Furthermore, 1D fibers can be used to weave fabrics to create sensing fabrics (e.g., Figure 1E ) or knitted into other shapes (e.g., Figure 1E1D fibers can be wound onto 3D structures, such as robotic hands, bodies, or organs. They can also be integrated with other materials, or even sewn into fabrics or tissues. In examples involving the use of such fibers with electronics [particularly those used for signal transmission for control or stimulation and / or detection of phenomena (e.g., sensors)], integration of associated circuitry with wireless communication systems is beneficial. In some exemplary experimental implementations, the core for winding the 1D structure is implemented as one of the following: 1D fibers, 1D hollow fibers, and a micro-patterned structure placed at or above the edge of a 2D structure (or sheet), which is then wound into the final 1D structure.

[0024] As illustrated in some examples in the figures, the post-processing (e.g., after winding or spiraling) form of the 1D structure can have several to a number of layers (e.g., 3-7 or 3-9) due to the overlapping portions after processing, depending on various exemplary structures. In other exemplary embodiments, the post-processing form of the 1D structure can have more than a few layers (e.g., 8-40) of overlapping portions, or only 1-2 overlapping layers, although this is not ideal for many applications. Other examples may have opposite sides of the post-processed portions that can meet at the edges, or meet almost at the edges without any overlap.

[0025] Consistent with certain examples according to this disclosure, another specific aspect of this disclosure is a method in which manufacturing processes occur on a 2D substrate, which is then wound into a 1D structure (such as...). Figure 1A (As shown). This layout design is applicable to various types of fibers, including versatile deformable bioelectronic fibers (t-BEF) that allow for precise control of the longitudinal, angular, and radial device position. The applications of the soft fibers disclosed herein are demonstrated, through experimental example implementations described herein, in highly dynamic and coiled GI environments and in the (living) brain.

[0026] Through discussion Figure 1A and related schematic diagrams ( Figure 1A-1H Exemplary methods of such manufacturing can be understood, and the figure, according to certain exemplary aspects of this disclosure, shows a 1D structure transformed into fibers by processing a 2D substrate with micropatterned components. In some examples, such 1D structures have been developed for bioelectronic fiber devices, achieving greater compactness and deformability, higher electronic component density, and better biosystem compatibility.

[0027] In one such experiment according to this disclosure, to fabricate such a device, the desired electronic components were microfabricated on a 2D thin film using conventional photolithography. Consistent with this, Figure 1BThis is a photograph of a 1.5 µm thick 2D film with a microfabrication apparatus for preparing high-density t-BEF. Subsequently, according to this disclosure, the 2D film is transformed into 1D fibers using a helical deformation method, such as... Figure 1C and 1D As shown. Figure 1C The image shows a high-density t-BEF (250 µm) containing 150 sensors (81 pressure sensors and 69 electrochemical sensors), demonstrating that the deformation from 2D to 1D resulted in a dramatic increase in device density per unit width (from 150 components per 3 cm width to 150 components per 250 µm diameter), and magnified views of the sensing components in sections i and ii. Figure 1D yes Figure 1C The microscopic image of the t-BEF shown illustrates partial interconnections and some surface sensors. The resulting fibers are soft and can be sewn into fabrics, knotted, bent, and stretched, as... Figure 1E The photographs of the fibers shown demonstrate the softness and flexibility of these bioelectronic fibers, allowing them to be sewn into fabrics, knotted, bent, and stretched against gelatin gels. In some of the processing described herein, the fiber diameter depends on the length and thickness of the 2D film, and its stiffness can be controlled by adjusting the diameter or selecting different skeleton materials. More specifically, Figure 1F This is a schematic diagram illustrating the size and deformation process of 2D thin films, which can be used to control the final fiber size; Figure 1G It is a graph showing the measured [emphasized (or red) circles near the dashed graph line] and calculated fiber diameter as a function of 2D film thickness and length (e.g., ...). Figure 1F The measured diameter is slightly higher than the calculated diameter, which may be due to the non-ideal packing at the beginning of the deformation process, resulting in a larger inner diameter (n=3). Figure 1H The chart shows the flexural stiffness of fibers prepared from different types of SEBS (with different Young's moduli: 1.2, 7.7, and 50.0 MPa) or different 2D film thicknesses (resulting in different fiber diameters: 0.18, 0.27, and 0.36 mm; n = 4).

[0028] It is worth noting that, in addition to the high density easily achievable through standard microfabrication on 2D thin films, helical deformation also increases component density (per unit width) by two to three orders of magnitude. For example, Figure 1D The 250 µm fiber shown is made from a 3 cm wide 2D film with 150 micropatterned sensing elements (e.g., Figure 1B (As shown). The component density per unit width changed from 150 / 30 = 5 mm⁻¹ to 150 / 0.25 = 600 mm⁻¹, and the density / width gain was 120.

[0029] refer to Figures 2A-2F An example of how the deformation process can be understood by dividing the method into two main parts: (i) the formation of the fiber core ( Figure 2A (ii) wound fibers ( Figure 2B In the first part or step, a core is formed by scraping the edge of the 2D film, which itself collapses and / or wrinkles, forming a "fiber" structure that can be used to initiate the winding process. This collapse and / or wrinkling is evident in the manufactured 1D structure (e.g., as shown in...). Figure 1A-1F and Figures 2A-2F (As shown in the diagram). This process depends on the thickness of the 2D film and its mechanical properties. Thin, soft, and highly self-adhesive films are easier to form a core. In the second part or step, deformation involves winding the film to achieve the final fibers. The winding process can be stopped before reaching the line contact area to facilitate connection to an external flat cable. In some examples, where appropriate, blades can be used for fiber winding to ensure tight contact between layers.

[0030] Figure 2B The forces involved in the process (along with the winding process) are also schematically shown, where F adh-ms It is the adhesion force between the film and the moving substrate, F adh-ss It is the adhesion force between the thin film and the stationary substrate, F adh-self It is the self-adhesive force of SEBS (or other elastomers used), F 卷绕 F is the force applied to the fiber to maintain the winding process. res F represents the force resisting the winding process (e.g., friction with a stationary substrate, winding resistance due to fiber deformation, etc.). comp It is the compressive force generated by the moving platform that helps maintain good adhesion between layers and prevents slippage.

[0031] In some experimental example implementations, this process has been optimized to achieve closely packed fibers with intact shape and structure, such as Figure 2CMicroscopic images show the winding process under different conditions. Ethylene-butadiene-styrene copolymer (SEBS) is used as the primary stretchable substrate due to its self-adhesive properties, which are utilized in both steps. While the adhesion between SEBS layers is sufficient to hold and bond the wound structure, an azide crosslinking agent, bis(6-((4-azido-2,3,5,6-tetrafluorobenzoyl)oxy)hexyl) sebacate, is also incorporated for further stabilization via thermal or UV crosslinking. Other elastic materials, such as styrene-butadiene-styrene copolymer (SBS), can also be successfully used according to this disclosure to prepare fibers (in some examples, the fibers post-treated (e.g., wound) can be made from a variety of elastic materials, not limited to styrene copolymers, such as styrene-ethylene-butadiene-styrene copolymer, poly(styrene-butadiene-styrene), styrene-isoprene rubber, silicone, polyurethane, acrylic block copolymers). In some examples, the wound structure can be made from flexible materials such as polyimide, polyethylene terephthalate, polycarbonate, and PMMA, combined with an adhesive layer.

[0032] The versatility of this deformation method allows for the preparation of fibers with different sizes and device layouts. For example, Figure 2D This is a set of 2D layout designs and corresponding fibers, demonstrating the versatility and control offered by this deformation method according to the present disclosure. Compared to previous methods, the exemplary method disclosed herein provides precise control over the longitudinal, angular, and radial component positions. Some components can be located on the surface based on their intended function, while others can be embedded within the fiber. Control over the fiber shape is also provided, and additional functions can be easily incorporated, such as fluid transport using hollow fibers or optical transmission by integrating optical fibers into the core. For example, Figure 2E A pair of images depicts advanced functionalities that can be integrated into fibers, including light guidance using fibers with optical waveguide cores (left) and fluid transport using hollow fibers (right).

[0033] Furthermore, this method can be extended to flexible substrates, such as polyimide. However, unlike self-adhesive elastic materials, flexible substrates require an additional adhesive layer to help maintain the rolled structure. Experimental work created electronic polyimide fibers containing multiple resistors. The resistance change after deformation was negligible, confirming the compatibility of the deformation process with non-stretchable substrates. As an example, Figure 2F An example of extending the exemplary deformation method to a flexible substrate is shown, in which polyimide fibers with multiple micropatterned resistor assemblies are prepared, and the resistance is measured before and after the winding process (without damage to the thin flexible film during deformation).

[0034] As a more specific example, some specific methods in this regard relate to apparatuses and methods related to the biomedical field, including: developing different types of endoscopes based on aspects of this disclosure; cheaper and more advanced gastrointestinal manometry devices (for indicating the ability of the esophagus to perform peristalsis), enabling more accurate and additional sensing and / or stimulation functions; developing electronic sutures for monitoring and accelerating wound healing; and integrating electronics onto existing 1D devices (guidewires and biopsy needles). Furthermore, other specific examples, also according to this disclosure, relate to apparatuses and methods related to biomedical fields (involving wearable devices and / or electronic textile technologies), for example, fiber-related aspects of this disclosure are used as building blocks for (e.g., advanced) electronic textiles and / or wearable technologies. As a specific example, according to certain other examples of this disclosure, high-density electronic components for body monitoring, on-body signal processing and signal (and related functional) manipulation, and subsequent computer-based data processing have been developed by using and / or integrating such aspects. As a specific example of such subsequent computer-based data processing, biomedical-related data collected using such fiber-based aspects were evaluated and correlated with previously known information about the subject (e.g., wearers of the relevant device or technology) or other subjects (e.g., subjects conforming to a specific demographic category) or related to the subject collecting the data. In this already very specific context, a more concrete example according to this disclosure is the continuous monitoring of human and animal performance in movement and other physical activities; for example, the technology is used in conjunction with implantable or wearable sensing devices (such as cardiac / lung electronic sensors) that utilize minute changes in strain, pressure, and / or capacitance to indicate changes in the subject's cardiac / lung function, and, according to such fiber-related aspects of this disclosure, in conjunction with interconnections (and / or combinations therewith) with such strain-related, capacitance-related, and / or pressure-related sensors (as disclosed in Annexes A, B, C, and / or D of potential U.S. provisional applications).

[0035] According to this disclosure, in some experimentally based exemplary embodiments, specific manufacturing methods have been used to create soft bioelectronic fibers for monitoring intestinal physiological signals and electrical stimulation, as well as recording single-nerve signals in the brain. While these experimentally based exemplary embodiments and related demonstrations focus on in vivo implantation, these works (and related findings) are applicable to the use and implementation of devices (e.g., equipment, systems, etc.) and methods suitable for a wide range of technologies and applications, including but not limited to smart fabrics, textiles, wearable devices, and soft robots.

[0036] In more specific examples, such aspects involve electronic devices and material-based sutures, long-term neural recordings, sutureable fibers for bowel stimulation, and electronic devices for alleviating irregular bodily functions [including, for example, irregular heart rhythms (e.g., other cardiac and / or lung-related functions), constipation and / or incontinence biological functions], one or more of these specific examples of which can be achieved by sensing biomedically specific functions of the object (e.g., electronic devices implanted near or above the object's membrane to sense signs of constipation or incontinence and responsively actuating (e.g., via another implanted device) or stimulating muscle / membrane tissue).

[0037] The discussion now turns to experimental examples of a multifunctional t-BEF for intestinal deployment. The 1D structure is well-suited for insertion into orifices and tubular structures in the human body. Based on certain experimental work, the GI channel was chosen as an example because its tortuous structure and continuous contraction facilitate the use of a soft and highly deformable device. Experimental work began with the development of a multifunctional t-BEF with several GI-related functional components, including strain / pressure and serotonin sensors, as well as electrostimulation electrodes. Eutectic gallium indium (EGaIn) was used for conductive interconnects due to its high conductivity and stretchability. All sensing components were fabricated from laser-induced graphene (LIG). The electrostimulation electrodes were fabricated using a dual network of poly(3,4-ethylenedioxythiophene)polystyrene sulfonate (PEDOT-PSS) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG) because of its high conductivity, low surface impedance, and good stretchability.

[0038] All electronic components were tested and characterized in vitro. The pressure and / or strain sensors according to this disclosure are based on LIG-based piezoresistors whose resistance varies with applied tensile and / or compressive forces. Experimental work recorded a good and reversible response to forces between 0.1 and 2 N. The pressure sensing t-BEF provides excellent longitudinal force distribution mapping, asymptotic force detection, and curvature information along different fiber locations. All of these may be relevant to the study of the biomechanics of GI tissues. For serotonin sensing, chronoamperometry or cyclic voltammetry was performed using LIG-based electrodes. Good sensitivity (0.332 nA / M) was obtained. -1 The estimated detection limits are ~24 nM. For stimulation, the low impedance of the PEDOT-PSS-based electrode enables high stimulation current (< 5 mA) at low voltages (< 4 V). Finally, the experimental work also demonstrates the possibility and capability of adding more components to the fiber, such as a pH sensor.

[0039] As the results of these experiments demonstrate, t-BEF is an ideal candidate for insertion into GI systems due to its high flexibility and isotropic deformability. This is supported, for example, by the fact that negligible disruption of movement was observed after inserting the fiber (250 µm in diameter, 1.7 MPa modulus) into an isolated mouse colon (ex vivo). Furthermore, insertion of the fiber into the colon of awake mice (in vivo) did not show any adverse effects on their behavior. Conversely, insertion into a polyimide rectangular film (a common plastic material used in implantable devices, with a modulus > 1 GPa) resulted in a significant reduction or delay in movement and marked rectal bleeding (i.e., blood appearing in fecal particles). Histological images further support these findings.

[0040] To highlight the versatility and longitudinal capabilities of the t-BEF, experimental work demonstrated simultaneous in vitro colonic motility sensing and stimulation in mice. The GI t-BEF with distributed pressure sensors can detect temporal and spatial motion signals with high precision. Notably, natural spatially progressive contraction events were observed and detected during the experiments. GI tissue was electrically stimulated using surface electrodes on the t-BEF, employing a previously reported biphasic stimulation method. Upon stimulation, an increase in motility events was observed from the response of the distributed piezoresistive sensors. This resulted in a significant increase in the motility index (defined as the average area under the peak motility recorded per minute) calculated from the sensory output of the t-BEF according to this disclosure. According to this disclosure, video analysis during the experiments also confirmed greater changes in colonic diameter and a higher frequency of events detected upon stimulation, including slow waves and the colonic migrating motor complex (CMMC). Additional colonic motility tests were also performed in mice (in anesthetized and freely moving conscious animals) using the GI t-BEF.

[0041] To verify the potential application of the t-BEF according to this disclosure in larger animal models, sensing and regulatory functions were investigated in the small intestine of a pig species. First, for natural motion sensing, a 10 cm sensing length t-BEF was inserted into the small intestine via laparotomy. Figure 3A-3L This is a set of schematic diagrams illustrating some exemplary aspects of this function (showing bioelectronic fibers in pigs), in which Figures 3A-3B The study demonstrates the deployment of t-BEF into the small intestine of pigs for monitoring and modulating GI signaling.

[0042] In this experiment, natural movement patterns were observed and recorded. Figure 3CNatural motion was recorded in the small intestine using a t-BEF equipped with eight pressure sensors. Progressive motion signals were observed (marked in yellow, see, for example, the S6 plot), with an estimated velocity of ~0.5 mm / s. Notably, the t-BEF (300 µm) is ~50 times smaller than the intestinal diameter, yet it was still able to reliably sense motion signals. Next, experimental work will involve designing a bifunctional t-BEF for both motion sensing and stimulation. Figure 3D This is a 2D design schematic of a dual-function t-BEF used for simultaneous motion sensing and stimulation. Figure 3E It displays from Figure 3D The image shows a photograph of the t-BEF obtained from the 2D design.

[0043] Figure 3F and 3G The response of the pressure sensor to contraction induced by a stimulus is shown. More specifically, Figure 3F The output of the pressure sensor in response to different stimulation voltages (n=7) is shown. The pressure sensor is located at the center of the stimulation electrode. Figure 3G It is a summary of the maximum responses obtained under different voltage stimuli.

[0044] A threshold of 2V is required to induce a significant contraction signal. This dual functionality enabled the experiment to successfully demonstrate closed-loop feedback programmable stimulation. Figure 3H This is a schematic diagram illustrating the induction of programmable contractile events in a long segment of the intestine using distributed stimulating electrodes. The distributed stimulating electrodes are used to stimulate specific parts of the tissue and program the process of contraction—similar to naturally occurring contractions. Simultaneously, distributed pressure sensors provide feedback on the location and progress of the contraction, such as… Figure 3I As shown, a closed-loop feedback system for programmable stimulation is illustrated, in which stimulation of the pig's intestine at different locations produces progressive contractions similar to natural movement patterns, and distributed pressure sensors provide feedback on the location and progress of the contractions. This system can be used to optimize electrical stimulation in real time.

[0045] The electrochemical sensing of serotonin in the small intestine of pigs was then demonstrated using laparoscopically delivered t-BEF. Figure 3J This illustration demonstrates the induction of serotonin release in the intestine using an SSRI injection. Changes in serotonin concentration can be detected using amperometric methods following injection of a selective serotonin reuptake inhibitor (from an SSRI). The presence of a serotonin peak is verified using cyclic voltammetry. Figure 3K The graph shows the drug-induced changes in intracavitary serotonin concentration using SSRI solution and PBS as controls (n = 7). Figure 3L The diagram illustrates the electrochemical sensing of SSRI-induced serotonin using cyclic voltammetry.

[0046] Certain implementations and experiments have successfully achieved high-density t-BEF recording for single-neuron recording. Single-unit neuron recording requires excellent electrical properties, including low interfacial impedance, small diameter, high-density recording pads, high shunt impedance of the dielectric, and low cross-coupling of the electrode traces. Experimental work using a high-density t-BEF according to this disclosure met all these requirements. Fibers were prepared using styrene-butadiene-styrene copolymer (SBS) as the substrate and encapsulant, and a dual network of PEDOT-PSS and PEG-PPG-PEG was used for the recording microelectrode. The microelectrode according to this disclosure exhibited very low impedance and high stability for at least one month. SBS encapsulation provided excellent insulation and was stable in PBS solution for at least one month. Through experimental work, a 32-channel 2D film with 20 µm x 20 µm PEDOT-based recording points was designed and fabricated, and then converted into the final neural t-BEF. See also Figure 4A and 4B These are schematic diagrams showing the 2D film design used to prepare the neural t-BEF. The magnified inset shows a microscopic image of the recording area. Figure 4B This is a microscopic image showing the tip of a neural t-BEF with recording PEDOT microelectrodes. The t-BEF has a 1.6 mm long recording area containing a set of tetrades spaced 40 µm apart. Since size can be important for minimizing insertion trauma, the experimental work involved designing the neural t-BEF with a pointed tip (150 µm in diameter). The microelectrodes are spirally distributed on the fiber surface to enable recording from all directions. After deformation, the microelectrodes according to this disclosure exhibit good impedance range and very high yield and consistency. Figure 4C The distribution of impedance measurements collected from 60 on-fiber microelectrodes is shown, demonstrating high yields after fabrication and deformation. To evaluate the ability of t-BEF to record neuronal activity, the experimental team implanted t-BEFs at various locations in the mouse brain (e.g., the hippocampus and prefrontal cortex). After a week of recovery, the mice were mounted on a treadmill for conscious head-fixation recording. Figure 4D This is a schematic diagram showing the setup used to record neural signals in awake mice. Spontaneous discharge activity (such as...) was observed. Figure 4E As shown, the raw data plots obtained from the four recording electrodes are displayed, revealing some spontaneous neural spikes (data were spike-sorted using Kilosort 2.43). Eight well-separated individual cells were identified, exhibiting a low proportion of interpeak spacing (ISI) violations (<0.3) and a high signal-to-noise ratio (SNR) of 5.01. Due to the high density, individual cells appear on multiple channels, as shown by the average of the spike triggers, and the waveform shapes are well-separated in UMAP space.

[0047] In addition, sharp wave ripples (SWRs) were detected, which are short bursts of oscillations in the hippocampus between 125 and 200 Hz, and are associated with memory consolidation and memory retrieval. Figure 4F This is an overlay map of hundreds of spikes collected via neural t-BEF (four distinct units are shown as detected by three different quadrupole electrodes). Figure 4G These are four correlation plots showing the probability of a second discharge after the initial spike. Figure 4H It is an ISI violation. Figure 4I-4J The spike ripples (SWRs) were detected in the hippocampus. The spectrogram showed a typical increase in power and observed ripples propagating longitudinally along the fibers, with stronger involvement in the CA1 and CA3 regions. Figure 4K -L is a spectrum showing a typical increase in power, including observations of ripples propagating longitudinally along the fiber, with stronger involvement in the CA1 and CA3 regions.

[0048] The following steps are performed in conjunction with other specific examples of the winding process for 2D structural deformation according to this disclosure. A 2D thin film (thickness ranging from 10 nm to 10 mm) is wound into a 1D structure with a diameter ranging from a few micrometers to tens of millimeters. The core can be designed by winding around a pre-formed fiber, wire, optical fiber, or tubing (e.g., a dissolvable core can be used to create one or more such tubing or internal structures). The core can be a micropatterned structure on the 2D thin film, and the winding process can use planar or non-planar structures [e.g., a planar 2D glass slide (moving platform, see...]. Figures 5A-5F (e.g., using glass, metal, plastic, and / or cylindrical rollers). Moving and stationary platforms (e.g.) Figures 5A-5F Surface modification (as shown) can be used to promote smooth winding and near-perfect layer stacking. Eccentric winding can be used to create pointed ends.

[0049] Figures 5A-5F This is a set of schematic diagrams illustrating certain exemplary aspects of this disclosure, wherein Figure 5A This is a schematic illustration of the first part of the deformation process, in which a 2D film is scraped to form a core that can later be used for winding. Figure 5B This is a schematic diagram illustrating the winding process and the forces involved, the adhesion between the film and the moving substrate, the adhesion between the film and the stationary substrate, and the self-adhesive force of SEBS (or other elastomers used). 卷绕 F is the force applied to the fiber to maintain the winding process. res F represents the force resisting the winding process (e.g., friction with a stationary substrate, rolling resistance due to fiber deformation, etc.). comp It is the compressive force generated by the moving platform that helps maintain good adhesion between layers and prevents slippage. Figure 5CThis demonstrates how different parameters (as shown throughout this disclosure) and F are adjusted. comp To optimize the winding process. Figure 5D The image depicts the tight interlayer adhesion after film deformation using thermal annealing. Figure 5E It is an image of eccentrically wound fibers, showing densely packed layers. Figure 5F The image shows a cross-section of the fiber, revealing layers that are well-bonded due to the self-healing properties of the elastic substrate.

[0050] According to the relevant experiments disclosed herein, ultra-high density fibers with a diameter of 230 micrometers and 1280 channels were also successfully fabricated.

[0051] Figures 6A-6H This is a set of schematic diagrams illustrating certain exemplary aspects of this disclosure relating to high-density electrical recording fibers, wherein Figure 6A These are photographs of a 2D film with 1280 channels before winding (part i shows a magnified image with 10 µm interconnects, and part ii shows a magnified image of the exposed recording area). Figure 6B yes Figure 6A Microscopic images of the exposed sites on the thin film, showing 10 recording electrodes. Figure 6C and 6D These are microscope images showing the 230 µm fibers obtained after winding. Figure 6E This is a cross-sectional image of the fiber, showing the different winding layers and Au / PEDOT interconnects. The inset shows the gold-based (e.g., Au / PEDOT) tracks, with some tracks marked by highlighted (red) lines. Figure 6F and 6G It is a 320-channel SEM image of the fiber. Figure 6H It is an impedance analysis curve, showing the good yield of 32 channels after the deformation process.

[0052] Therefore, some of the experimental examples described above provide a direct strategy for fabricating high-density and multifunctional bioelectronic fibers. This method involves transforming a 2D thin film with microfabrication devices into 1D fibers using helical deformation. This allows for the direct use of conventional fabrication methods and leverages various procedures already developed for devices, sensors, and circuits. The developed t-BEF offers a substantial improvement in functional component density compared to planar flat devices. This work demonstrates for the first time thin electronic fibers with precise control over the angular, radial, and longitudinal position of the device. The platform described in this work not only exhibits superior flexibility but also surpasses existing electronic fibers in terms of size, density, and functionality. Furthermore, the GI t-BEF according to this disclosure has numerous advantages compared to other motion-sensing probes currently available for the GI channel. In the context of neural recording, the t-BEF according to this disclosure exhibits unprecedented flexibility compared to existing microelectrode arrays. While the various demonstrations according to this disclosure primarily focus on in vivo implantation, these findings have enormous potential for a wide range of applications, including smart fabrics, textiles, wearables, and soft robotics.

[0053] Now we turn to some materials used in conjunction with the experimental example implementations and aspects disclosed above. The four types of Tuftec™ SEBS (H1062, H10521, H1052, H1221) were purchased from Asahi Kasei Corporation. Poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT PSS, product # 739332), SBS (product # 182877), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) diacrylate (PEG-PPG-PEG DA, product # 915858), lithium phenyl-2,4,6-trimethylbenzoylphosphonate (product # 900889), phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO, product # 511447), pentaerythritol tetra(3-mercaptopropionate) (PETMP, product # 381462), dimethyl sulfoxide (DMSO, product # 276855), 25% nitric acid (product # 1.60317), EGaIn (product # 495425), AgNO3 (product # ) 209139), KNO3 (product # 221295), FeCl3 (product # 157740), PVB (product # P110010), dextran (product # 31417), a solution containing Nafion™ 117 (product # 70160), and aniline (product # 242284) were purchased from Sigma-Aldrich, USA. Photoresist (AZ® 1512) was purchased from MicroChemcials, UK. Microposit™ developer MF-CD-26 was purchased from Micro Resist Technology GmbH, Germany. Polyimide solution (PI2611) was purchased from HD MicroSystems. The polyimide film (Kapton® polyimide film, electronic grade, 12" wide, 0.0050" thick, 12" long) was purchased from McMaster-Carr.

[0054] Regarding fabrication and characterization, the above-disclosed experimental example embodiments and aspects relate to the preparation and deformation of 2D thin films into fibers. An aqueous solution of dextran (50 mg / ml, 1000 rpm, 1 min) was spin-coated onto a plasma-treated Si wafer and baked at 150 °C for 5 min. Then, a toluene solution of SEBS was spin-coated, followed by baking at 130 °C for 10 min. 2D thin films of different thicknesses were prepared using different concentrations of SEBS (150 mg / ml, 100 mg / ml, and 50 mg / ml). Thin films of different moduli were created using different types of SEBS (H1062, H10521, H1052, H1221). The 2D thin films were then released from the Si wafer by immersion in water for 1 hour and transferred to Si treated with octadecyltrichlorosilane (OTS). The samples were then dried at 70 °C for 1 hour. The edges were cut using a laser cutter. The deformation process was then initiated by scraping the edges of the film with a glass slide to form the core of the fibers. Once a core of 30-50 micrometers is obtained, a winding process is initiated using a glass slide as a moving platform to obtain the final fiber. The fiber is then annealed in a vacuum at 100 °C.

[0055] To control the adhesion between the 2D film and the stationary substrate, Si wafers treated with OTS or plasma are used. The winding process cannot proceed properly on plasma-treated Si because it causes the 2D film to tear. Plasma treatment is used to control the adhesion between the moving platform and the formed fibers. Furthermore, a controlled manual atmospheric pressure is applied during winding to tighten the stacking of different fiber layers. High adhesion (between the moving platform and the fiber core) and low pressure can lead to fiber slippage and improper fiber winding.

[0056] The experimental example embodiments and aspects described above also relate to the fabrication of optical and fluid transport fibers. For optical fibers, a 2D thin film of SEBS is prepared as previously described. A 250 µm PMMA fiber (AZIMOM PMMA plastic-terminated light-emitting fiber) is used as the core to begin the winding process, skipping the scraping portion of the deformation process. For fluid transport fibers, a 2D thin film of SEBS is prepared and cut. Then, a polypropylene glycol (PPG)-based polyurethane (PPG-PU) film is sprayed next to the SEBS, with a very small overlap. The winding process begins from the PPG-PU side, eventually forming the fiber core. The fiber is annealed in a vacuum at 100 °C and then developed in acetone to dissolve the PPG-PU core and obtain a hollow SEBS fiber.

[0057] The above-described experimental example embodiments and aspects also relate to the preparation of polyimide fibers. For the preparation of polyimide fibers, a diluted polyimide solution (diluted with NMP 1:1.5) was directly spin-coated (5000 rpm, 1 min) onto an OTS-treated Si wafer. Then, PPG-PU (50 mg / ml in IPA) was spin-coated (2000 rpm, 1 min) as an adhesive layer. SEBS or PPG-PU was sprayed onto the edges of the 2D film to form a wound fiber core. This step is necessary because, as described in the section on elastic films, the polyimide film cannot be scraped into a fiber core.

[0058] The experimental examples and aspects described above also relate to the preparation and characterization of LIGs. LIGs, which constitute the main sensing components, were generated using direct laser carbonization of a polyimide substrate. Kapton films were laser-etched using an Epilog Fusion M2 CO2 laser, following a reported laser-induced graphene method. A laser power of 7.5 W and a scan rate of 30% were used. For morphological and compositional characterization of the LIGs, SEM images were acquired using a FEI XL30 Sirion SEM (5 kV). Raman spectroscopy was performed using a LabRAM HR Evolution microscope [HORIBA Scientific] with excitation wavelengths of 532 or 633 nm and a grating of 1,800 grooves mm. -1 .

[0059] The experimental examples and aspects described above also relate to mechanical property characterization. The mechanical properties of bioelectronic SEBS fibers were investigated using an Instron 5565 (100-N load cell). Samples of different diameters (e.g., from 150 µm to several hundred µm, such as 180 µm, 350 µm, and 550 µm) or made of different types of SEBS (H1062, H1052, H1051, H1221) were tested. Samples were bonded between compression plates. Fiber lengths were measured using calipers. Thickness was measured using an optical microscope. Mechanical testing was performed using a strain rate of 10 mm / min.

[0060] The above-described experimental examples and aspects also relate to the characterization of the electrical and mechanical properties of EGaIn. To measure the conductivity of the EGaIn electrode during tensile testing, a sample was attached to a homemade tensile stage connected to an LCR meter [Keysight Technologies E4980]. Silver epoxy resin was used for contact. The contact area was sealed with TorrSeal® epoxy resin to prevent strain in that area. A 0.5 × 20 mm size was used. 2The EGaIn trajectory was used to measure the resistance under 0-50% stretching (in 5% steps).

[0061] The experimental example embodiments and aspects described above also relate to the preparation of GI t-BEF. A dextran (50 mg / ml) aqueous solution was spin-coated (1000 rpm, 1 min) onto a Si wafer and baked at 150 °C for 5 min. Then, a SEBS (80 mg / ml) toluene solution containing 4% (w / w) of an azide-based crosslinking agent (bis(6-((4-azido-2,3,5,6-tetrafluorobenzoyl)oxy)hexyl) sebacate) was spin-coated (1000 rpm, 1 min). This was followed by baking at 150 °C for 10 min. The desired functional components (LIG and PEDOT-PSS sensing / stimulation interfaces and EGaIn interconnects) were then patterned on the SEBS film (described in detail in the next section). Finally, the SEBS encapsulation layer was patterned using a shadow mask by spraying (1 ml of 25 mg / ml SEBS solution). The film was annealed in vacuum at 135 °C for 5 hours. 2D sheets containing functional components are released from Si wafers by immersion in water for 1 hour and then transferred to OTS-treated Si. The samples are then dried at 70 °C for 1 hour. Edges are cut using a laser cutter, and the film is then manually wound using a glass slide. The bonding area is left unwound for subsequent connection to a flexible flat cable. After bonding and sealing, the fibers are further modified, such as by silver and PANI electrodeposition, immersion in FeCl3, and coating with PVB and Nafion (described in detail in the next section) to obtain the desired sensing components. The fibers are annealed in a vacuum at 100 °C before use.

[0062] The experimental example implementations and aspects described above also relate to the patterning of EGaIn interconnects. Photoresist was spin-coated (2500 rpm, 45 sec) onto a substrate spin-coated with SEBS, followed by exposure (385 nm) using a Durham MagnetoOptics ML3 MicroWriter. After exposure, the photoresist was developed for 1 min. Then, gold (30 nm) was thermally evaporated on the surface to provide an adhesion layer between EGaIn and SEBS. EGaIn was screen-printed onto the surface using PDMS. This process was repeated several times until a smooth EGaIn film was obtained. The sample was immersed in acetone for 30 min, followed by sonication for 30 seconds. This process was repeated until the photoresist layer was completely removed.

[0063] The experimental example implementations and aspects described above also relate to the fabrication and characterization of pressure / strain sensors. LIG was transferred from a polyimide substrate to a 2D SEBS film by applying pressure and shear force using a metal scraper. EGaIn interconnects were then patterned to form a resistor used as a piezoresistive pressure / strain sensor, followed by SEBS encapsulation. After film release and winding, the sensor was finally positioned at the desired location on the fiber. For such devices, the LIG network deforms under the applied force, resulting in a change in resistance. The performance of these sensors was examined using different tests: i) applying normal forces (0.1 N–20 N) directly to the sensor using a force gauge. ii) manually rolling a metal cylinder on the fiber at different speeds to generate a progressive force. iii) Demonstration of force sensing within a tube: a fiber was inserted into a Tygon tube (Tygon® E-3603; wall thickness: 0.062 inches; outer diameter: 0.5 inches; modulus: 12.1 MPa). An external force was applied to the tube wall to induce structural deformation, simulating what occurs in the intestine. Resistance was measured and correlated with the degree of force applied. In each test, the current (at 0.5 V) was recorded using a PalmSens4 [PalmSens BV, Netherlands].

[0064] Experimental example implementations and aspects also relate to the fabrication and characterization of a serotonin sensor. Serotonin sensing was performed using a two-electrode electrochemical apparatus. The working electrode was based on a LIG embedded in the SEBS surface (prepared via transfer from polyimide). Nafion was electrodeposited onto the serotonin sensing electrode according to previously reported methods to minimize the influence of interfering molecules, such as ascorbic acid. Briefly, the electrode was immersed in a Nafion solution and held at a constant voltage (1 V) relative to a commercial reference electrode for 30 seconds. The electrode was rinsed with water and dried at 100 °C for 10 minutes. For the reference electrode (located at the tip after fiber winding), an Ag / AgCl-based electrode was prepared by electrodepositing silver onto the LIG in an aqueous solution of 5 mM AgNO3 and 1 M KNO3. The LIG surface electrode was immersed in the electrodeposition solution. The potential was then scanned from -0.9 V to 0.9 V (relative to the Ag electrode) in 20 segments at a scan rate of 0.1 V s⁻¹.47. After rinsing with water, the silver surface was immersed in a FeCl3 solution (3M) to form AgCl. Finally, the electrode was stabilized by covering it with a PVB layer after immersion in a methanol solution of PVB (50 mg / ml). After the 2D film was deformed into a fiber, the serotonin sensor on the fiber was characterized in vitro using chronoamperometry (0.5 V) or cyclic voltammetry (-0.4 to 1.3 V, 10 V / sec, 0.001 V step) at different concentrations (100, 200, 400, and 800 nM). To test the effect of bending on serotonin sensing, the response to different concentrations (0, 1 μM, and 2 μM) of serotonin was monitored in a flat state and after the fiber was bent around a plastic tube with a radius of 2 mm.

[0065] Experimental example implementations and aspects also relate to the fabrication and characterization of the pH sensor. For pH sensing, a potentiometric apparatus with a two-electrode cell was used. The working electrode was based on polyaniline (PANI)-modified LIG. PANI was electrodeposited using a previously reported method. The previously described reference electrode was also used here. pH dependence was measured because PANI is known to be sensitive to pH due to varying degrees of doping. This inherent sensitivity was used to translate pH values ​​into changes in open-circuit potential (OCP). The pH sensor was characterized in a variety of buffer solutions with pH values ​​ranging from 3 to 10. OCP was measured for 30 seconds in each solution. Measurements were paused when the electrode was transferred from one solution to another.

[0066] The above-described experimental examples and aspects also relate to the preparation and characterization of PEDOT-PSS-based stimulating electrodes. A PEDOT-PSS solution [PEDOT-PSS (1.1%, in H2O), PEG-PPG-PEG DA, and lithium phenyl-2,4,6-trimethylbenzoylphosphonate (100:1:0.05 wt%, respectively)] was prepared and stored in a refrigerator. Before use, 10 µl of a fluorinated surfactant (Capstone™ FS-30) and 50 µl of DMSO were added to each 1 gram of solution. The final mixture (0.5 ml) was sprayed onto the surface to obtain the stimulating interface by laser-cutting a shadow mask. The film was cured under UV light [American Ultraviolet, Inc.] for 20 min, followed by baking at 135 °C for 10 min. The film was also immersed in methanol for 1 min, followed by baking at 135 °C for 2 min. The film was then immersed in nitric acid (25%) for 30 seconds, rinsed with water, and dried on a hot plate (135 °C) for 1 minute. EGaIn was then patterned to form interconnects, followed by encapsulation with a SEBS layer. For characterization, two PEDOT-PSS-based stimulation electrodes were immersed in PBS. Impedance was measured from 1 MHz to 1 Hz. Stimulation current was also measured under biphasic stimulation conditions: 5 ms pulse duration at different voltages of 0.5, 1, 2, and 4 volts (V).

[0067] The above-described experimental example embodiments and aspects also relate to the preparation of neural t-BEF. An aqueous solution of dextran (50 mg / ml) was spin-coated (1000 rpm, 1 min) onto a Si wafer and baked at 150 °C for 5 min. Then, a toluene solution of SBS (80 mg / ml) containing 4 wt% PETMP and 4 wt% BAPO was spin-coated (1000 rpm, 1 min). The film was cured under UV for 1 min. It was then baked at 135 °C for 10 min. The film was cooled and immersed in toluene for 3 min to remove any unreacted residues. It was then baked at 135 °C for 2 min and subjected to plasma treatment. The PEDOT-PSS base electrode was then patterned. The previously described PEDOT-PSS solution was spin-coated (1000 rpm, 90 s) onto the plasma-treated SBS film. The film was cured under UV for 20 min and then baked at 135 °C for another 10 min. The film was immersed in methanol for 1 min and then baked at 135 °C for 2 min. A very thin layer of SEBS (10 mg / ml in toluene, 2500 rpm, 1 min) was spin-coated to achieve better adhesion between PEDOT and the subsequent photoresist layer. After baking (135 °C, 1 min), the photoresist layer was spin-coated (2500 rpm, 45 s), followed by exposure using a Durham Magneto-Optics ML3 MicroWriter (385 nm, 90 mJ / cm). 2 The exposed PEDOT layer was etched using plasma etching [March Instruments PX-250 plasma ashing machine, 150W, 250 seconds]. The film was then immersed in acetone and sonicated for 30 seconds to remove the photoresist layer, followed by development with cyclohexane to remove any remaining SEBS. The PEDOT-PSS electrode was then immersed in nitric acid (25%) for 30 seconds, rinsed with water, and dried on a hot plate (135 °C) for 1 minute. The SBS was then directly photo-patterned for encapsulation. In short, an SBS solution (80 mg / ml in toluene) was spin-coated and etched using an ML3 MicroWriter (385 nm, 350 mJ / cm). 2Exposure was performed. The film was baked at 90 °C for 2 minutes, then developed with cyclohexane at 2500 rpm for 45 seconds. This step was repeated to achieve a double-layer SBS encapsulation with a total thickness of 3.2 μm. The film was baked at 135 °C for 10 minutes. The 2D sheet containing all recording electrodes was released from the Si wafer by immersion in water for 1 hour and transferred to OTS-treated Si. The sample was then dried at 70 °C for 1 hour. The edges were cut using a laser cutter. After cutting, the film was manually wound using a glass slide. The film has a varying width (the width is smallest in the recording area), which results in finer tips for the fibers. The bonding area was left unwound for subsequent connection to a flexible flat cable. After bonding and sealing, the fibers were annealed overnight in vacuum at 100 °C before use.

[0068] Impedance testing was also used in the experimental example implementations and aspects described above. For long-term size-dependent impedance testing, four sizes of PEDOT electrodes (25 µm x 25 µm, 50 µm x 50 µm, 100 µm x 100 µm, and 200 µm x 200 µm) were fabricated. Impedance was measured from 1 MHz to 1 Hz relative to commercially available platinum wire. This test was performed at different time points after immersion (immediately, 1 week, 2 weeks, and 1 month). For encapsulation testing, a fully encapsulated (double-layer 3.2 μm thick SBS) PEDOT-PSS base electrode was used. Impedance was measured from 1 MHz to 1 Hz relative to commercially available platinum wire to demonstrate the robustness of the encapsulation. This test was also performed at different time points (immediately, 1 week, 2 weeks, and 1 month). For fiber microelectrode impedance testing, the impedance of 32 microelectrodes on fibers was measured from 1 MHz to 1 Hz in PBS solution relative to platinum wire electrodes.

[0069] Such experimental examples of implementation methods and aspects also involve gastrointestinal studies and in vivo motion sensing and stimulation in anesthetized pigs. All surgical procedures in mice and pigs were performed according to protocols (32497, 32778, and 31893) approved by the Stanford University Institutional Animal Care and Use Committee (IACUC).

[0070] This study used 6-9 week old, 10 kg female juvenile Yucatan pigs (Sus scrofa) from S&S Farm [Ramona, CA]. All pigs were fasted overnight, underwent general anesthesia with volatile isoflurane, and were connected to vital signs monitors during the terminal surgery. A midline laparotomy was made to expose the viscera. Krebs / PBS buffer was injected into the pig intestine to flush out contents before sensing. The suspensory ligament of the duodenum was identified to locate the duodenum and jejunum, and the ileocecal valve was located to identify the ileum. To record spontaneous movement, a soft 10 cm long fiber (with 8 pressure sensors) was inserted into the small intestinal lumen through a stoma for continuous real-time recording. Spontaneous movement was very infrequent and unpredictable due to the effects of anesthesia. For electrical stimulation, a bifunctional fiber (with 5 stimulation electrodes and 5 pressure sensors) was used. Baseline movement was recorded for 30 seconds, followed by biphasic stimulation at 2V and 4V (5 ms stimulation pulse, 10 s period). The experiment was conducted in multiple intestinal locations in three pigs (n=7). Distributed sensors were used to sense pressure for programmable stimuli. Selective stimulation was applied at three different locations.

[0071] The experimental example implementation and aspects described above also involve the electrochemical sensing of serotonin in anesthetized pigs. This study used 6–9-week-old female juvenile Yucatan miniature pigs (Sus scrofa) weighing 10 kg each from S&S Farm [Ramona, CA]. Briefly, all pigs were fasted overnight, underwent general anesthesia using volatile isoflurane, and were connected to vital signs monitors during the terminal surgery. A midline laparotomy was made to expose the viscera. PBS solution was injected into the pig intestine to flush out the contents. The suspensory ligament of the duodenum was identified to locate the duodenum and jejunum, and the ileocecal valve was located to designate the ileum. A soft 10 cm long t-BEF (with 5 serotonin sensors) was inserted into the small intestinal lumen through a stoma for continuous recording. Baseline stabilization was performed for 10 minutes after PBS injection (0.5 ml). A new baseline was recorded for 1 minute after 10 minutes. The SSRI solution (10 µM, 0.5 ml) was then administered directly intraluminally upstream of the sensing area. Measurements were taken 10 minutes after injection. The experiment was conducted in multiple intestinal segments of three pigs (n=5). After recording, the anesthetized animals were euthanized by trained researchers. Data were collected simultaneously from all five sensors. However, only a few sensors responded; that is, some sensors showed no change after SSRI injection, while others responded strongly. This is presumably related to the distance of the fibers from the intestinal wall or their orientation, which was not well controlled in this experiment and is known to affect sensitivity to serotonin. A single sensor may not accurately capture all concentration changes due to its localized measurement. However, by employing multiple sensors, they have the advantage of distribution and provide a more reliable average concentration based on multiple readings.

[0072] To verify that the signal originated from serotonin, cyclic voltammetry was used. As previously described, the fiber was inserted into the intestine. After injection of PBS (0.5 ml), baseline stabilization was performed for 10 minutes using continuous cyclic voltammetry (V: -0.4 to 1.3 V, scan rate: 10 V / sec). After 10 minutes, a new baseline was recorded, defining the background current in the intestine. SSRI solution (10 µM, 0.5 ml) was then administered upstream of the sensing area via direct intraluminal injection. Measurements were taken immediately after injection and 10 minutes later, showing the appearance of serotonin peaks. To further confirm that these peaks originated from serotonin, serotonin hydrochloride solution (10 µM, 0.5 ml) was injected, and the peaks (obtained after SSRI injection) were observed to be larger.

[0073] Statistical analysis was also used. For data analysis, Origin, MATLAB, and Excel were used. All repetitions, error bars, p-values, and statistical tests are indicated in the legends.

[0074] The focus now shifts to brain research related to the aforementioned experiments, beginning with neurosurgery (all experiments performed on mice were approved by the Stanford Laboratory Animal Care Committee). Stanford's animal care and use program meets the requirements of relevant federal and state regulations governing the humane care and use of laboratory animals, including the USDA Animal Welfare Act and the Public Health Service policy on the humane care and use of laboratory animals. Stanford's laboratory animal care program is accredited by the Association for Assessment and Certification of Laboratory Animal Care. All mice were housed at the Stanford Veterinary Services Center under a reverse 12-hour dark / 12-hour light cycle (temperature: 20°C to 25°C; humidity: 50% to 65%), with free access to food and water as needed. All experiments were conducted within their activity cycles. Anesthesia was induced using isoflurane (4%; maintained at 1.5%). After anesthesia, the mice's heads were fixed to a stereotactic wheel (RWD) frame, and body temperature was maintained using a heating pad (Keenovo). Eyes were protected with puralube ointment. The skull was exposed, and a 0.5 mm diameter cranial window was created at the following coordinates (distance from the anterior fontanelle): hippocampus: 1.7 mm anteroposteriorly; 1.6 mm mid-laterally; prefrontal cortex: 2 mm anteroposteriorly; 0.5 mm mid-laterally. A dura mater was then performed. A fiber optic device was then inserted at a speed of 0.1 mm / s to a target depth of 3 mm (this depth for both the hippocampus and prefrontal cortex), and the cranial window was subsequently filled with Kwik-Sil (WPI). A self-tapping bone screw was fixed to the cerebellum as a grounding electrode, and a stainless steel headbar was secured to the skull using dental adhesive (C&BMetabond). Following implantation, mice were allowed to acclimatize to running on a treadmill for 7 days.

[0075] For electrophysiological recording, mice were placed on treadmills and secured to head clips. Probes were then connected to the data acquisition system (Intan RHS stimulation / recording system) via a custom adapter plate. Electrophysiological data were collected at 30 kHz for 10 minutes. Data analysis was performed using custom software written in MATLAB 2019b (MathWorks). Spike sorting was performed using Kilosort 2.0 (https: / / github.com / MouseLand / Kilosort) with default parameters. Subsequently, quality metrics were calculated and duplicate spikes were removed using the ecephys spike sorting pipeline (https: / / github.com / AllenInstitute / ecephys_spike_sorting) within ±0.16 ms. Clustering was then manually performed in Phy (https: / / github.com / cortex-lab / phy). Individual cells were classified as good only if the ISI violation was less than 0.3, the number of spikes was greater than 200, and the presence rate was greater than 0.9.

[0076] Those skilled in the art will also recognize the various terms used in this disclosure based on their literal meaning. As an example, this specification may describe and / or illustrate aspects that contribute to the implementation of the examples by various semiconductor materials / circuits, which may be shown or described using terms such as layer, block, module, device, system, cell, controller, and / or other circuit types. Such semiconductors and / or semiconductor materials (including portions of semiconductor structures) and circuit elements and / or associated circuitry may be used in conjunction with other elements to illustrate how certain examples are performed in terms of structure, steps, functions, operations, activities, etc. It is also understood that terms used to indicate orientation, such as up / down, left / right, top / bottom, and above / below, may be used herein to refer to the relative positions of elements shown in the figures. It should be understood that these terms are used for ease of labelling only, and in actual use, the disclosed structures may have different orientations than those shown in the figures. Therefore, these terms should not be interpreted in a restrictive manner.

[0077] Based on the foregoing description and illustrations, those skilled in the art will readily recognize that various modifications and variations can be made to the various embodiments without strictly adhering to the exemplary embodiments and applications illustrated and described herein. For example, the example method shown may involve steps performed in various sequences, retaining one or more aspects of the embodiments herein, or may involve fewer or more steps. Such modifications do not depart from the true spirit and scope of all aspects of this disclosure, including those set forth in the claims.

[0078] Therefore, various specific details are set forth in the following description to describe the specific examples presented herein. However, it will be apparent to those skilled in the art that one or more other examples and / or variations thereof may be practiced without following all the specific details set forth below. In other instances, well-known features have not been described in detail so as not to obscure the description of the examples herein. For ease of illustration, the same reference numerals may be used in different figures to refer to the same elements or additional instances of the same elements. Furthermore, although in some cases aspects and features may be described in separate figures, it should be understood that features from one figure or embodiment may be combined with features from another figure or embodiment, even if such combination is not explicitly shown or described as a combination. Similarly, unless otherwise stated, range (any and all measures) is only an example of “approximate range”, where the term can be understood as the degree to which the boundaries of the range (e.g., using improved and / or reduced component, material, or circuit-based design parameters) change by 10-20% (or in some cases by 5-35%), and, in the case of improvements compared to previously reported work, the degree of improvement is 20% or higher.

[0079] As an example, this specification describes and / or illustrates aspects that contribute to the realization of the claimed disclosure by various components, circuits, or lines of equipment that may be illustrated or described using terms such as block, module, device, system, unit, controller, and / or other component-related, circuit-related, and / or material-based descriptions (e.g., including material layers containing doped semiconductor materials). As a specific example, “microfabrication equipment” is exemplified and / or refers to one or more circuit-related components, such as very small integrated components and / or circuits (e.g., “microchips”), fabricated based on micro-component unit operations (as a more specific example, “microfabrication equipment” is exemplified and / or refers to the process of fabricating small structures at the micrometer or smaller scale). Such components may include or refer to those discussed above herein, and may also include (but are not limited to): capacitors, resistors, electrodes, insulating materials between electrodes, circuits, or micropatterned sensing components, and circuit-based structures including one or more such components, such as one or more sensors for sensing / detecting pressure, capacitance, and / or strain. Furthermore, according to this disclosure, "high density" in the context of manufacturing refers to or includes the density of materials, components, etc., which can be at least five times, one order of magnitude, and / or two to three orders of magnitude higher than the density achievable by known (standard) microfabrication techniques (as illustrated in the aforementioned U.S. provisional application). For example, Appendix A discusses using helical deformation according to aspects of this disclosure to increase component density (per unit width) by up to two and three orders of magnitude, and in one such example, 250 µm fibers were obtained from a 3 cm wide 2D film having 150 micropatterned sensing components, and the component density per unit width varied to varying degrees.

[0080] Such components, circuits, and / or materials are used in conjunction with other elements to illustrate how certain implementations can be performed in terms of structure, steps, functions, operations, activities, etc.

Claims

1. An apparatus, the apparatus comprising: 1D fiber material, characterized in that, It has a fiber structure with one or more of the following deformations: helix, curl and pleat.

2. The device of claim 1, further comprising one or more of the following embedded within the 1D fiber material: microfabricated electronic components; and electronic devices.

3. The apparatus of claim 1, further comprising one or more of the following fixed to the 1D fiber material: micro-machined electronic components; and electronic devices.

4. The apparatus of claim 1, further comprising one or more line contact areas adjacent to and not connected to the 1D fiber material, configured and arranged for contacting the 1D fiber material.

5. The apparatus of claim 1, further comprising one or more line contact regions adjacent to and connected to the 1D fiber material.

6. The apparatus of claim 1, further comprising one or more circuits integrated with the 1D fiber material, the circuits including at least one sensor to sense parameters in response to at least one of the following changes: pressure, capacitance, and strain.

7. The apparatus of claim 1, further comprising a polymer-based substrate (polymer, such as SEBS), the substrate having self-adhesive properties and at least one property selected from the group consisting of: stretchability; and elasticity that allows it to recover its original shape after stretching.

8. The apparatus of claim 1, wherein the 1D fiber material is further characterized by having a plurality of micropatterned circuit components disposed between overlapping portions of the 1D fiber material, wherein the thickness or diameter of the 1D fiber material is in the range of 150 μm to several hundred μm.

9. A method, the method comprising: A 1D fiber material is provided, characterized in that it has a fiber structure selected from one or more of the following deformations: helix, crimp, or pleat.

10. The method of claim 9, wherein the 1D fiber material is integrated with at least one microfabrication component or device, and the method further comprises: The 1D fiber material is formed using a soluble rigid structure, and then the rigid structure is dissolved. Controlling the position of the 1D fiber material involves at least one of the following: longitudinal, angular, and radial-based positions.

11. The method of claim 9, wherein the 1D fiber material is integrated with at least one micromachining component or device, and the method further includes controlling the position of the 1D fiber material, involving at least two of the following: longitudinal, angular, and radial-based positions.

12. The method of claim 9, wherein the 1D fiber material is integrated with one or more interconnects, and the provision of the 1D fiber material includes at least one of: inducing the one or more deformations; using the 1D fiber material to sense at least one of the following changes: pressure, capacitance, and strain; and testing one or more conductive properties of the 1D fiber material.

13. The method of claim 9, wherein the 1D fiber material provided comprises at least one of the following: Real-time mapping of biomedical signals obtained from living organisms through the 1D fiber material; and tissue stimulation within living organisms.

14. The method of claim 9, wherein: The 1D fiber material is integrated with a circuit including at least one micro-processed component and / or device; as well as The 1D fiber material also includes: real-time mapping of biomedical signals obtained from living organisms through the 1D fiber material, and stimulation of tissues in living organisms, wherein the circuitry is used to facilitate the real-time mapping and the stimulation of tissues.

15. A method, the method comprising: 1D fiber materials are deformed into fiber structures with one or more of the following characteristics: helix, crimp, and pleat.

16. The method of claim 15, further comprising: The core material is formed from 2D fiber material; The core material is given one or more features by at least one of the following: rotating the core material; winding the core material; And to cause the core material itself to collapse to provide wrinkles.

17. The method of claim 15, wherein the 1D fiber material is integrated with one or more selected from microfabricated electronic components and electronic devices, and the method further comprises using the 1D fiber material for one or more biomedical functions selected from: motion mapping, serotonin sensing; single-neuron recording of brain activity; tissue stimulation within the gastrointestinal (GI) system; and recording the response of a microelectrode array.

18. The method of claim 15, wherein the 1D fiber material is integrated with one or more selected from microfabricated electronic components and electronic devices, and the method further comprises using the 1D fiber material for one or more biomedical functions selected from: monitoring physiological parameters or responses in a living organism; and introducing or inducing biomodulation in a curved or confined region of a living organism.

19. The method of claim 15, further comprising using a core-based structure to transform or wind the 1D structure, wherein the core comprises one or more of the following: 1D fibers, 1D hollow fibers, and micropatterned structures disposed at or above the edge of a 2D structure or sheet, the 2D structure or sheet subsequently formed or shaped to correspond to the structure of the 1D fiber material.

20. The method of claim 15, wherein the 1D fiber material is integrated with one or more circuit elements selected from microfabricated electronic components and electronic devices, and the method further comprises using microfabrication techniques to form the one or more circuit elements, the techniques relating to at least one of patterning, deposition, and photolithography.

21. A method, the method comprising: A 1D fiber material is provided, characterized in that it has a fiber structure with one or more deformations selected from: helix, crimp, or pleat, wherein: The 1D fiber material is integrated with a circuit including at least one microfabricated component and / or device, and is configured to transmit signals indicating one or more biomedical functions selected from: monitoring physiological parameters or responses in a living organism; and introducing or inducing biomodulation in a curved or confined region of a living organism; and The use of 1D fiber materials also includes: real-time mapping of biomedical signals obtained from living organisms via 1D fiber materials, and stimulation of living tissues, wherein the circuitry is used to facilitate the real-time mapping and the stimulation of tissues.

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