Fluorinated elastomers for brain probes and other applications

Abstract

Articles and devices comprising fluorinated polymers and methods of making fluorinated polymers are generally described. In some cases, such fluorinated elastomers can be used for sensing neural activity, for example, by encapsulating electronic circuitry or other applications. Further, according to certain embodiments, the polymers can be surprisingly deposited directly onto a layer comprising a low molecular weight fluorinated polymer, for example, without swelling in the presence of certain solvents. Some embodiments generally relate to devices and methods for treating fluorinated polymers and subsequently depositing materials onto the treated fluorinated polymers. This can allow for the fabrication and patterning of multilayer articles comprising fluorinated elastomers.

Description

[0001] Related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 159,623, entitled “Perfluorinated Elastomers for Brain Probes and Other Applications,” filed March 11, 2021; and U.S. Provisional Application No. 63 / 290,732, entitled “Fluorinated Elastomers for Brain Probes and Other Applications,” filed December 17, 2021, the entire contents of which are incorporated herein by reference for all purposes. Technical Field

[0003] This section provides a general description of articles and methods related to fluorinated elastomers.

[0004] background

[0005] Decoding neural signals is crucial for bridging the existing knowledge gap between our understanding of behavioral neuroscience and the molecular understanding of synaptic circuits. Potential applications of advanced neural interface technologies include a general understanding of neurodegenerative diseases or brain circuits, as well as increasing the bandwidth of brain-computer interfaces for novel medical devices such as neural prostheses or deep brain stimulators. However, probing the dynamics of neural networks on sufficiently large spatial and temporal scales to understand neural coding requires simultaneously measuring tens of thousands, or even hundreds of thousands, of neurons in vivo over time. Furthermore, each neuron itself can have tens of thousands to hundreds of thousands of synaptic connections that can extend throughout the entire brain. Therefore, long-term stable and whole-brain activity mapping is needed to understand the brain's connectome.

[0006] Various microelectrode array techniques have been developed to simultaneously measure unit extracellular action potentials in hundreds to thousands of neurons over periods ranging from weeks to months. However, further increases in the density of electrical sensors such as microelectrodes or transistors are limited by immune responses caused by mechanical mismatches between probes and brain tissue. Therefore, improvements are needed.

[0007] Overview

[0008] Articles and methods relating to fluorinated elastomers are generally described. In some cases, the subject matter of the invention relates to a variety of different uses of interrelated products, alternative solutions to specific problems, and / or one or more systems and / or articles.

[0009] One aspect generally relates to an article. According to some embodiments, the article comprises: a first layer comprising a first fluorinated polymer; a second layer bonded to the first layer; and a third layer bonded to the second layer, comprising a second fluorinated polymer.

[0010] On the other hand, it generally relates to an article of manufacture. In some embodiments, the article of manufacture comprises: a substrate configured for implantation into an organ of a subject, the substrate including a plurality of electrodes, the substrate including a first layer comprising a first fluorinated polymer, a second layer bonded to the first layer, and a third layer comprising a second fluorinated polymer bonded to the second layer.

[0011] Another aspect generally relates to an article of manufacture. In some embodiments, the article of manufacture comprises: a substrate including a plurality of electrodes, the substrate including a first layer comprising a first fluorinated polymer, a second layer bonded to the first layer, and a third layer comprising a second fluorinated polymer bonded to the second layer, having a density greater than or equal to 10. -9 Electrodes / micrometer 2 The proportion.

[0012] Another aspect generally relates to an article of manufacture. In some embodiments, the article of manufacture comprises: a substrate including a plurality of electrodes, the substrate including a first layer comprising a first fluorinated polymer, a second layer bonded to the first layer, and a third layer comprising a second fluorinated polymer bonded to the second layer, wherein the number density of the electrodes is greater than or equal to 10. -3 Electrodes / micrometer 2 .

[0013] Another embodiment generally relates to an article of manufacture. In some embodiments, the article of manufacture comprises: a substrate including a plurality of electrodes, the substrate including a first layer comprising a first fluorinated polymer, a second layer bonded to the first layer, and a third layer comprising a second fluorinated polymer bonded to the second layer, wherein the overall elastic modulus of the substrate is less than or equal to 10. 6 Pa.

[0014] Another aspect generally relates to an article of manufacture. According to some embodiments, the article of manufacture comprises: a first layer comprising a first fluorinated polymer; a second layer bonded to the first layer; and a third layer comprising a second fluorinated polymer bonded to the second layer; wherein the third layer has an average thickness H in micrometers, and wherein the polymer on the substrate is immersed in a 10xPBS solution at 65°C for at least 1*H. 2 The device exhibited a reduction of no more than 50% in specific electrochemical impedance modulus (i.e., electrochemical impedance modulus normalized to the geometry of the sample) at 1 kHz.

[0015] One aspect generally relates to an article comprising a first layer comprising a perfluoropolyether; a second layer bonded to the first layer; and a third layer bonded to the second layer, comprising a perfluoropolyether.

[0016] On the other hand, it generally involves an article comprising a perfluoropolyether with a weight-average molecular weight of less than 8 kDa, wherein the perfluoropolyether is located on a semiconductor substrate.

[0017] Another aspect generally relates to an article comprising a polymer on a substrate comprising a crosslinked perfluoropolyether, wherein the polymer exhibits at least 10 when formed into an article having a minimum size of at least 0.3 micrometers after being immersed in 1,3-bis(trifluoromethyl)benzene for more than or equal to 9 seconds, dried in nitrogen, and measured at 1 kHz. 6 ohm-m specific electrochemical impedance modulus.

[0018] Another aspect generally relates to an article comprising a polymer on a substrate, said polymer comprising a crosslinked perfluoropolyether, wherein the polymer on the substrate exhibits a reduction of no more than 50% in specific electrochemical impedance modulus at 1 kHz after immersion in a phosphate buffer solution for 100 days.

[0019] On the other hand, the method generally relates to a method. In some embodiments, the method includes inserting a substrate comprising a plurality of electrodes into an organ of a subject, the substrate comprising a first layer comprising a first fluorinated polymer, a second layer bonded to the first layer, and a third layer comprising a second fluorinated polymer bonded to the second layer.

[0020] Another aspect generally relates to a method. In some embodiments, the method includes: depositing a fluorinated polymer on a substrate; applying an inert gas plasma to the fluorinated polymer to form a treated fluorinated polymer; and depositing material onto the treated fluorinated polymer.

[0021] Another aspect generally relates to a method. In some embodiments, the method includes: depositing a fluorinated polymer on a substrate; treating the fluorinated polymer to facilitate deposition; and depositing a second fluorinated polymer onto the treated fluorinated polymer.

[0022] One aspect generally relates to a method. In some embodiments, the method includes: depositing a fluorinated polymer on a substrate; treating the fluorinated polymer to facilitate deposition; and depositing material forming a plurality of electrodes onto the treated fluorinated polymer.

[0023] On the other hand, it generally involves a method. In some embodiments, the method includes: determining electrical signals from a plurality of electrodes on a substrate at least partially contained within a subject, wherein the substrate includes a first layer comprising a first fluorinated polymer, a second layer bonded to the first layer, and a third layer comprising a second fluorinated polymer bonded to the second layer.

[0024] Another aspect generally relates to a method. In some embodiments, the method includes: using an electrode on a substrate that has been in contact with the single cell for at least 5 days to determine the electrical activity of the single cell within a living subject, wherein the substrate comprises a layer containing a fluorinated polymer.

[0025] Another aspect generally relates to a method. In some embodiments, the method includes: determining electrical signals from a plurality of electrodes on a substrate at least partially contained within the subject, wherein the substrate has a polarity of less than or equal to 10. 6 Pa total elastic modulus and includes a layer containing fluorinated polymer.

[0026] One aspect generally relates to a method. In some embodiments, the method includes: electrically stimulating cells within a subject using a plurality of electrodes on a substrate, wherein the substrate includes a first layer comprising a fluorinated polymer, a second layer bonded to the first layer, and a third layer comprising a fluorinated polymer bonded to the second layer.

[0027] On the other hand, a method is involved, comprising depositing a perfluoropolyether on a substrate; applying argon plasma to the perfluoropolyether to form a treated perfluoropolyether; and depositing material onto the treated perfluoropolyether.

[0028] Other advantages and novel features of the invention will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying drawings. In the event of any conflicting and / or inconsistent disclosures in this specification and in documents incorporated by reference, this specification shall prevail.

[0029] Brief description of the attached figures

[0030] Non-limiting embodiments of the invention will be described by way of example with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale unless otherwise stated. In the drawings, each identical or nearly identical component is generally represented by a single number. For clarity, not every component is labeled in every figure, nor is every component of every embodiment of the invention shown, where illustration is not necessary for those skilled in the art to understand the invention. In the drawings:

[0031] Figure 1 A cross-sectional schematic diagram of an exemplary article comprising a perfluorinated polymer according to certain embodiments is presented;

[0032] Figure 2 A cross-sectional schematic diagram of an experimental apparatus for measuring impedance according to certain embodiments is presented;

[0033] Figure 3 Methods for preparing articles comprising perfluorinated polymers according to certain embodiments are presented;

[0034] Figures 4A-4D The results of specific electrochemical impedance measurements of polymer films according to certain embodiments are presented;

[0035] Figure 5AAn illustrative method for determining the ion concentration of a polymer according to certain embodiments is presented;

[0036] Figure 5B An exemplary concentration distribution of ions is presented after a polymer pre-equilibrated with buffer is exposed to deionized water;

[0037] Figures 5C-5D Compare the ion desorption of polymer layers according to certain embodiments at different temperatures;

[0038] Figure 5E The ionic conductivity of polymer layers determined by different measurements according to certain embodiments was compared;

[0039] Figure 6 Equations for determining ionic conductivity according to certain implementation schemes are presented;

[0040] Figures 7A-7C Compare the temperature dependence of intrapolymer ionic behavior according to certain implementation schemes;

[0041] Figure 8 Exemplary methods for preparing articles comprising perfluorinated polymers according to certain embodiments are presented;

[0042] Figures 9A-9B An exemplary nitrogen diffuser according to certain embodiments is presented;

[0043] Figure 10A The specific electrochemical impedance modulus of polymers according to certain embodiments was compared;

[0044] Figure 10B The mechanical properties of the polymer according to certain embodiments are presented:

[0045] Figure 10C The elastic modulus and electrochemical stability of polymer materials according to certain embodiments were compared;

[0046] Figure 11A An exploded perspective view is presented of an exemplary article of an invention designed for use as a neural sensor according to certain embodiments;

[0047] Figure 11B-11E Images of exemplary articles designed for use as neural sensors according to certain embodiments are presented;

[0048] Figure 12A-12B The resistance of the metal electrodes according to certain embodiments is shown;

[0049] Figures 13A-13B The impedance behavior of articles comprising an uncalibrated electrode and an electrode coated with PEDOT:PSS according to certain embodiments was compared.

[0050] Figure 14 Photographs are presented of a plastic frame for holding the device according to certain embodiments;

[0051] Figures 15A-15B The insertion of the device into the brain of a living, moving mouse is shown according to certain embodiments;

[0052] Figures 16A-16E The signals collected from the device implanted in the brain of a live mouse are presented;

[0053] Figures 17A-17C The results of specific electrochemical impedance measurements of polymer films according to certain embodiments are presented;

[0054] Figure 18 A method for preparing articles comprising fluorinated polymers according to certain embodiments is presented;

[0055] Figure 19 Images of exemplary articles designed to be used as neural sensors according to certain embodiments are presented;

[0056] Figure 20 The changes in the electrochemical impedance modulus of the electrode after coating with a conductive material according to some implementation schemes are presented;

[0057] Figure 21 The electrochemical impedance modulus of a polymer on an exemplary electrode according to some embodiments is presented as a function of time.

[0058] Figure 22 The electrode number density and elastic modulus of various neural sensors according to some embodiments were compared with those of neural sensors prepared according to the embodiments described herein;

[0059] Figure 23 A schematic diagram of an exemplary stripping test according to some implementation schemes is presented;

[0060] Figure 24 The adhesion energy of the polymer layer at different peel rates according to certain embodiments is presented;

[0061] Figure 25 The interconnect resistance of exemplary brain probes according to certain embodiments is shown;

[0062] Figure 26 A schematic cross-sectional view of a multilayer article according to certain embodiments is presented;

[0063] Figure 27 Exemplary bending stiffness of a simulated multilayer article according to certain embodiments is presented;

[0064] Figure 28The ratios between the flexural stiffness of different exemplary multilayer articles as a function of the number of metal layers according to certain embodiments are presented;

[0065] Figures 29A-29B Implantation of an exemplary neural sensor substrate according to some implementation schemes is presented;

[0066] Figure 30 Exemplary measurements using multiple exemplary electrodes implanted in the brain of a subject, according to some implementation schemes, are presented;

[0067] Figure 31 Exemplary results are presented of peak potential sorting analysis of measurements performed using multiple exemplary electrodes implanted in the brain of a subject, according to some implementation schemes;

[0068] Figure 32 An exemplary mapping of measurements using multiple exemplary electrodes according to certain embodiments is presented, wherein the measurements are represented according to principal component space;

[0069] Figure 33A The average noise associated with the electrodes is presented over a 10-week period following the implantation of an exemplary sensor into the brain of a subject, according to certain implementations.

[0070] Figure 33B The average peak potential amplitude across all channels of the electrode is presented over a period of 10 weeks following the implantation of an exemplary sensor into the brain of a subject, according to certain implementation schemes.

[0071] Figure 34 Exemplary fluorescence measurements of the immune response of subjects to implanted brain probes according to certain implementation schemes are presented.

[0072] Detailed description

[0073] Large-scale whole-brain neuronal activity mapping is crucial for deciphering neuronal population dynamics in neuroscience, understanding and alleviating neurological disorders, and constructing high-bandwidth brain-computer interfaces (BMIs) for neural repair and communication. Ultimately, the goal of brain mapping is to simultaneously record the activity of millions or even billions of neurons in a long-term stable manner at single-cell, millisecond spatiotemporal resolution. "Tissue-like" thin-film electronics with subcellular characteristic sizes and tissue-level flexibility enable implantation without glial cell proliferation, recording stable neuronal activity over long periods at single-cell, single-peak spatiotemporal resolution, suitable for neuroscience, bioelectronic medicine, and brain-computer interfaces (BMIs). A major challenge is scaling up the number of microelectrodes in tissue-like electronics without using rigid materials that are fundamentally incompatible with the mechanical properties of the brain. Another challenge is the tendency for soft electronics to degrade in the brain's chemical environment, which degrades most polymeric materials over time. Articles and sensors containing fluorinated polymers offer significant advantages for electronic devices such as neural implants. For example, fluorinated polymers can possess the electrical and / or mechanical properties required for brain implants and can exhibit excellent long-term stability under physiological conditions.

[0074] This disclosure recognizes the importance of fluorinated polymers for brain implants and provides inventive methods for preparing multilayer articles comprising multiple layers of fluorinated polymers. These articles can exhibit some of the superior properties of fluorinated polymers. For example, some exemplary non-limiting articles described herein contain per micrometer 2 10 -3 One electrode and / or having less than or equal to 10 6 Total elastic modulus per Pa. According to some implementation schemes, per micrometer... 2 This number of electrodes represents a tenfold increase in electrode area number density relative to sensors with comparable elastic moduli. Furthermore, according to some embodiments, this elastic moduli represents per micrometer... 2 The elastic modulus of brain sensors with a comparable number of electrodes is reduced to one-thousandth.

[0075] While nanofabrication techniques can be used to produce bioelectronic components for in vivo use, the long-term stability of these devices under physiological conditions, and the mismatch between their mechanical properties and those of human tissue, limits the scope of these technologies. In some embodiments, fluorinated polymers (e.g., perfluorinated polymers) have been identified as a way to address these limitations. Therefore, in some aspects, this disclosure generally relates to perfluorinated polymers with long-term stability under near-physiological conditions, which can be used in a variety of articles and devices. For example, in some embodiments, these perfluorinated polymers are used in implants, such as as a coating. In some embodiments, the invention generally relates to fluorinated polymers, including fluorinated polymers with long-term stability, such as perfluorinated polymers. In some embodiments, these fluorinated polymers are used in implants, such as as a coating.

[0076] Some aspects of this disclosure relate to systems and methods for preparing fluoropolymers, including articles containing such polymers, such as devices, sensors, implants, circuits, coated substrates, etc. Other aspects of this disclosure relate to systems and methods for preparing perfluoropolymers, including articles containing such polymers, such as devices, sensors, implants, circuits, coated substrates, etc. Without wishing to be bound by any theory, it is believed that the superhydrophobicity of perfluoropolymers can make the manufacture of articles and devices containing perfluoropolymers challenging. Therefore, in one embodiment, this disclosure relates to a method of treating perfluoropolymers (e.g., perfluoropolyethers) that unexpectedly allows the deposition of additional materials bonded to the perfluoropolymer. Perfluoropolymers can be treated by applying plasma (e.g., argon plasma). In some cases, the additional material is an additional perfluoropolymer that can increase the total thickness of the perfluoropolymer layer. Therefore, in some embodiments, the manufacture of surprisingly thick perfluoropolymer layers (e.g., thicker than 300 nanometers) is disclosed. This surprising thickness can advantageously improve the stability and / or mechanical properties of perfluoropolymers in electronic devices. In contrast, other technologies cannot produce such a thick layer of perfluorinated polymer on articles or devices.

[0077] In some aspects, this disclosure relates to articles and / or devices comprising fluoropolymers. For illustrative purposes, a non-limiting example is provided herein. Other embodiments are possible as described in more detail below. In some aspects, this disclosure relates to articles and / or devices comprising perfluoropolymers. For example, some embodiments relate to the manufacture of articles having perfluoropolymers. For example, an article may have a first layer of perfluoropolymer (e.g., perfluoropolyether), a second layer bonded to the first layer (e.g., aluminum, gold, etc.), and a third layer of perfluoropolymer (e.g., perfluoropolyether) bonded to the third layer. For example, Figure 1An article 100 is shown, having a first layer 102 of a perfluorinated polymer, a second layer 104 bonded to the first layer 102, and a third layer 106 of a perfluorinated polymer bonded to the second layer 104. Such an article can cover at least a portion of an electronic circuit, or other applications such as those described herein. In some cases, such articles and circuits can prove usable as components of bioelectronic devices. As mentioned above, layered perfluorinated polymers have not been previously described.

[0078] However, it should be understood that these examples are presented for illustrative purposes rather than for limitation; other aspects and implementation schemes are also discussed below.

[0079] Certain aspects of this disclosure relate to polymers, particularly perfluorinated polymers. According to some embodiments, the polymer is a fluorinated polymer. For example, the polymer can be a perfluorinated polymer, such as a polymer in which carbon atoms in a portion of the polymer are bonded only to fluorine and / or other heteroatoms rather than hydrogen. The polymer can also be a fluorinated but not perfluorinated polymer, as described in more detail below. In some embodiments, the polymer comprises or is substantially composed of a perfluorinated polyether. The polymer can be any suitable perfluorinated polyether. For example, the polymer may comprise perfluorinated polyether (PFPE), polytetrafluoroethylene (PTFE), perfluorinated polyether dimethacrylate (PFPE-DMA), fluorinated ethylene-propylene (FEP), perfluoroalkoxy polymer (PFA), or polychlorotrifluoroethylene (PCTFE). The polymer can be a copolymer, such as tetrafluoroethylene propylene (TFE). For example, in some embodiments, the polymer is perfluorinated polyether dimethacrylate.

[0080] Articles and apparatus comprising perfluorinated polymers, as well as methods for preparing perfluorinated polymers, are generally described. In some cases, such perfluorinated elastomers can be used to sense neural activity, for example, by encapsulating electronic circuits, or for other applications. Furthermore, according to certain embodiments, polymers can be surprisingly deposited directly onto layers comprising low molecular weight perfluorinated polymers, for example, without swelling in the presence of certain solvents. Some embodiments generally relate to apparatus and methods for treating perfluorinated polymers and subsequently depositing material onto the treated perfluorinated polymer. This can allow for the fabrication and patterning of multilayer articles comprising perfluorinated elastomers.

[0081] Such polymers can reduce or inhibit the passage of ions in a variety of applications (e.g., implants), as ions that can enter may lead to degradation of such articles or devices. For example, perfluorinated polymers can be present on at least a portion of the substrate of an article or device. As discussed herein, in some embodiments, such perfluorinated polymers can be used to inhibit the passage of ions in various articles or devices, such as those implanted in a subject or exposed to physiological conditions. For example, degradation in such polymers can be quantified by measuring the specific electrochemical impedance modulus (i.e., the electrochemical impedance modulus normalized to the geometry of the sample) over a long period of time (e.g., when exposed to physiological conditions). For example, in one assay, such polymer films with a thickness equal to or less than 1 μm could surprisingly retain most (e.g., more than 50%) of their specific electrochemical impedance modulus after immersion in phosphate buffer solution for more than 100 days.

[0082] Without being bound by any theory, it is believed that the hydrophobicity of perfluorinated polymers can make the manufacture of articles and devices containing perfluorinated polymers challenging. Therefore, in one embodiment, this disclosure relates to a method of treating perfluorinated polymers (e.g., perfluoropolyethers) that unexpectedly allows for the deposition of additional materials bonded to the perfluorinated polymer. Perfluorinated polymers can be treated by applying plasma (e.g., argon plasma). In some cases, the additional material is an additional perfluorinated polymer that can increase the total thickness of the perfluorinated polymer layer. Thus, in some embodiments, the manufacture of surprisingly thick perfluorinated polymer layers (e.g., thicker than 300 nanometers) is disclosed. For example, polymer layers with a thickness greater than 3 micrometers can be manufactured. This surprising thickness can advantageously improve the stability and / or mechanical properties of perfluorinated polymers in electronic devices. In contrast, other techniques cannot produce such thick perfluorinated polymer layers on articles or devices.

[0083] In another embodiment, certain properties of the perfluorinated polymer are controlled by crosslinking the perfluorinated polymer. In some embodiments, this property control can beneficially improve the performance of the perfluorinated polymer as a component of articles and devices. For example, certain crosslinked polymers, such as those described herein, can be used to achieve properties such as reduced electrical properties or ion transport. However, it should be understood that crosslinking is not a requirement in all embodiments.

[0084] In some embodiments, the polymer is a non-perfluorinated fluorinated polymer. For example, the fluorinated polymer may be a partially fluorinated polymer. In some embodiments, the fluorinated polymer is fluorinated to a concentration greater than or equal to 25%, greater than or equal to 50%, greater than or equal to 75%, or more. In some embodiments, the fluorinated polymer is fluorinated to a concentration less than or equal to 100%, less than or equal to 90%, less than or equal to 75%, less than or equal to 50%, or less. Combinations of these ranges are also possible. For example, in some embodiments, the fluorinated polymer is fluorinated to a concentration greater than or equal to 25% and less than or equal to 100%.

[0085] The polymer can be any of a variety of suitable fluorinated polymers. For example, in some embodiments, the polymer can be poly(1,1,1,3,3,3-hexafluoroisopropyl acrylate) (PHFIPA) or poly[2-(perfluorohexyl)ethyl]acrylate (PPFHEA). The polymer can also be a copolymer (e.g., a copolymer between two or more fluorinated polymers, including both these polymers and the aforementioned perfluorinated polymers).

[0086] In the context of this disclosure, it has been recognized that fluoropolymers can be difficult to process, and this can negatively impact their use. Therefore, certain aspects relate to improved processing of fluoropolymers, such as perfluorinated polymers. For example, according to some embodiments, fluoropolymers can be coated and photo-patterned onto a substrate or other polymer layer, for example, using added spacers and / or nitrogen diffusers. In some embodiments, material can be deposited on top of the fluoropolymer, for example, by treating the fluoropolymer, which can promote adhesion between the fluoropolymer and subsequently deposited material.

[0087] In some embodiments, depositing material onto a fluoropolymer layer is important for manufacturing relatively thick and / or multilayer articles comprising a fluoropolymer (e.g., a perfluorinated polymer), as discussed herein. In some embodiments, the fluoropolymer may be treated. For example, some embodiments include applying plasma (e.g., argon plasma) to the fluoropolymer to form a treated fluoropolymer, as described in further detail below. Surprisingly, in some embodiments, treatment of the fluoropolymer can advantageously facilitate material deposition onto the surface of the fluoropolymer.

[0088] Specifically, in some embodiments, this disclosure relates to the processing of perfluorinated polymers. It has been recognized that perfluorinated polymers can be difficult to process, and this can negatively impact their use. Therefore, certain aspects relate to improved perfluorinated polymers. For example, according to some embodiments, perfluorinated polymers can be coated onto a substrate or other polymer layer, for example, using added spacers and / or nitrogen diffusers. In some embodiments, material can be deposited on top of a perfluorinated polymer (e.g., perfluoropolyether), for example, by treating the perfluorinated polymer, which can promote adhesion between the perfluorinated polymer and subsequently deposited material.

[0089] In some embodiments, depositing material onto a perfluorinated polymer layer is important for manufacturing relatively thick and / or multilayer articles comprising the perfluorinated polymer, for example, as discussed herein. In some embodiments, the perfluorinated polymer may be treated, for example. For example, some embodiments involve applying plasma (e.g., argon plasma) to the perfluorinated polymer (e.g., perfluoropolyether) to form a treated perfluorinated polymer (e.g., perfluoropolyether), as described in further detail below. Surprisingly, it is recognized that, in some embodiments, treatment of the perfluorinated polymer can advantageously facilitate material deposition onto the surface of the perfluorinated polymer.

[0090] Some implementations generally involve relatively thick and / or multi-layered articles that are resistant to degradation. For example, in some implementations, thick and / or multi-layered articles may be used in implantable devices. In some cases, such articles may be resistant to degradation by aqueous solutions.

[0091] For example, polymers and / or articles containing polymers can be immersed in an aqueous solvent (e.g., brine) for a period of time. When immersed in an aqueous solvent, some polymers and / or articles containing polymers discussed herein are able to maintain a high specific electrochemical impedance modulus, which can be used to demonstrate that the polymers and / or articles can partially or completely suppress ion transport through them.

[0092] Without being bound by theory, according to certain embodiments, reduced ion transport in a polymer can lead to a significant decrease in the ionic conductivity passing through the polymer, reducing degradation and resulting in improved dielectric properties. In some embodiments, the polymer (e.g., perfluorinated polymers) undergoes a phase transition at a phase transition temperature. For example, according to certain embodiments, polymers (e.g., perfluoropolyethers) contain more crystalline phase at lower temperatures. Without being bound by theory, greater ion transport in the phase may be found at temperatures above the phase transition temperature. Some polymers discussed herein experience phase transition temperatures close to physiological temperatures (e.g., within + / -1°C, + / -2°C, + / -3°C, or + / -5°C of 37°C). According to certain embodiments, the presence of a phase transition close to physiological temperatures may be related to reduced ion transport through the polymer under physiological conditions.

[0093] In some cases, a high specific electrochemical impedance modulus can indicate that the polymer and / or articles containing the polymer will be more stable in vivo. According to some embodiments, this can be determined by immersing the polymer and / or articles containing the polymer in an aqueous solution (e.g., a phosphate buffer solution) for a period of time; according to some embodiments, the polymer may experience only a small decrease in specific electrochemical impedance modulus even after immersion for a long period of time, such as at least 100 days, or other times discussed herein.

[0094] For example, according to certain embodiments, the polymer exhibits a value greater than or equal to 1 × 10⁻⁶ when immersed in an aqueous solvent during article formation. 6 ohm-m, greater than or equal to 2×10 6 ohm-m, greater than or equal to 3x10 6 ohm-m, greater than or equal to 5 x 10 6 ohm-m, or higher, specific electrochemical impedance modulus. According to certain embodiments, when forming an article, the polymer exhibits a specific electrochemical impedance modulus greater than or equal to 25%, greater than or equal to 50%, greater than or equal to 75%, greater than or equal to 90%, greater than or equal to 95%, or greater than or equal to 99% or more of its original specific electrochemical impedance modulus after immersion in an aqueous solvent. In other words, the article containing the polymer exhibits a slight decrease in specific electrochemical impedance modulus even after immersion in an aqueous solvent for a period of time, such as at least 100 days, or other times discussed herein, which demonstrates that the polymer and / or the article can suppress ion transport. For example, according to certain embodiments, the article containing the polymer, after immersion in an aqueous solvent for a period of time, such as at least 100 days, or other times discussed herein, may exhibit a decrease in specific electrochemical impedance modulus less than or equal to 75%, less than or equal to 50%, less than or equal to 25%, less than or equal to 10%, less than or equal to 5%, less than or equal to 1%, etc., of its original specific electrochemical impedance modulus.

[0095] Generally, impedance can be expressed as a complex quantity, as is known to those skilled in the art. For example, electrochemical impedance can be described as having an electrochemical impedance modulus (the magnitude of the impedance) and a phase (the phase angle of the complex quantity). The electrochemical impedance modulus depends on the geometry and can be normalized by the sample geometry to produce a specific electrochemical impedance modulus. For example, in embodiments comprising a homogeneous polymer having an area and a thickness, the specific electrochemical impedance modulus of the homogeneous polymer is the electrochemical impedance modulus of the homogeneous polymer multiplied by the area of ​​the polymer and divided by the thickness of the polymer. Normalization allows for comparisons between samples with different geometries. According to some embodiments, the area of ​​the polymer is known. For example, in some embodiments, the area of ​​the polymer used to calculate the specific electrochemical impedance modulus may be equal to the area of ​​the conductive material disposed beneath the polymer. The thickness of the polymer can be determined by any suitable technique, including, for example, using a stylus profilometer, scanning electron microscope, atomic force microscope, or X-ray reflectometer.

[0096] Electrochemical impedance spectroscopy (EIS) is typically measured at a specific frequency. For example, in some embodiments, EIS is measured at 1 kHz, 2 kHz, 5 kHz, or 10 kHz. EIS can be measured using any suitable technique. For instance, those skilled in the art will know that EIS can be measured using a standard three-electrode setup, such as... Figure 2 As shown. An exemplary procedure for measuring electrical impedance is described in Example 2 below.

[0097] According to some embodiments, the aqueous solvent includes a phosphate buffer solution. In some embodiments, the concentration of the phosphate buffer solution (PBS) is greater than or equal to 0.5x, 1x, 2x, 3x, 5x, 8x, or 10x of the standard PBS concentration (0.1M). In some embodiments, the concentration of the phosphate buffer solution (PBS) is less than or equal to 15x, 12x, 10x, 8x, 5x, or 3x of the standard PBS concentration (0.1M). Here, a solution of phosphate buffer solution with a standard PBS concentration of 10x is referred to as 10x phosphate buffer solution or 10x PBS. Combinations of these ranges are possible. For example, according to some embodiments, the phosphate buffer solution has a concentration greater than or equal to 0.5x and less than or equal to 15x. According to some embodiments, the aqueous solution is 1x PBS. In some embodiments, the aqueous solution is 10x PBS.

[0098] In some embodiments, immersion occurs at a temperature. According to some embodiments, the immersion temperature is greater than or equal to 20°C, greater than or equal to 25°C, greater than or equal to 30°C, greater than or equal to 35°C, greater than or equal to 37°C, greater than or equal to 40°C, greater than or equal to 45°C, greater than or equal to 50°C, greater than or equal to 50°C, greater than or equal to 40°C, greater than or equal to 37°C, or lower. Combinations of these ranges are possible. For example, according to some embodiments, the immersion temperature is greater than or equal to 20°C and less than or equal to 90°C.

[0099] According to some embodiments, polymers may experience a slight decrease in their specific electrochemical impedance modulus after immersion in an aqueous solvent for a period of time, for example, a decrease of less than 5%, or other decreases as described herein. For example, polymers may experience a slight decrease in their specific electrochemical impedance modulus after immersion for 5 days or more, 6 days or more, 7 days or more, 8 days or more, 9 days or more, 10 days or more, 15 days or more, 25 days or more, 50 days or more, 100 days or more, 150 days or more, 200 days or more, 250 days or more, 300 days or more, 350 days or more, 400 days or more, 450 days or more, 500 days or more, or longer. Combinations of these ranges with the foregoing ranges are possible. For example, according to some embodiments, polymers exhibit a decrease in specific electrochemical impedance modulus of less than or equal to 50% at 1 kHz after immersion in a phosphate buffer solution for 100 days or more. As another example, according to certain embodiments, after soaking in a phosphate buffer solution for 450 days, the polymer exhibits a decrease in specific electrochemical impedance modulus of no more than 50% at 1 kHz. As yet another example, according to certain embodiments, after soaking in a 10x phosphate buffer solution at 70°C for 5 days, the polymer exhibits a decrease in specific electrochemical impedance modulus of no more than 50% at 1 kHz.

[0100] According to some embodiments, after immersing the polymer in an aqueous solvent for a period of time, related to the average thickness H (in micrometers) of the polymer within the article, the polymer may experience a slight decrease compared to the electrochemical impedance modulus. For example, in some embodiments, the polymer is immersed in an aqueous solvent at a temperature greater than or equal to 1*H. 2 Day, greater than or equal to 2*H 2 Day, greater than or equal to 3*H 2 Day, greater than or equal to 4*H 2 Day, greater than or equal to 5*H 2Day, greater than or equal to 10*H 2 After days or longer, the polymer experiences a slight decrease compared to its electrochemical impedance modulus. In some embodiments, the polymer exhibits a resistance of less than or equal to 100 H⁺ ions upon immersion in an aqueous solvent. 2 Day, less than or equal to 50*H 2 Day, less than or equal to 20*H 2 Day, less than or equal to 10*H 2 After a day or less, the polymer experiences a slight decrease compared to the electrochemical impedance modulus. Combinations of these ranges are possible. For example, in some embodiments, the polymer exhibits a resistance greater than or equal to 2*H in aqueous solvents. 2 And less than or equal to 100*H 2 The subsequent immersion exhibits a slight decrease compared to the electrochemical impedance modulus. Combinations of these ranges with the aforementioned ranges are also possible. For example, according to some embodiments, immersion in a 10x phosphate buffer solution at 65°C with a modulus greater than or equal to 1*H... 2 After 1 day, the polymer exhibited a decrease in specific electrochemical impedance modulus of less than or equal to 50% at 1 kHz.

[0101] According to certain embodiments, the degradation resistance of a polymer can be related to its crosslinking. Any suitable crosslinking chemical can be present within the polymer. Therefore, according to certain embodiments, the polymer (e.g., a perfluoropolyether) can contain a crosslinking agent. For example, according to one set of embodiments, perfluoropolyether dimethacrylate (PFPE-DMA) contains two methyl acrylate substances, each of which, according to certain embodiments, can undergo a crosslinking reaction. Thus, for example, in some embodiments, perfluoropolyether dimethacrylate (PFPE-DMA) can be crosslinked by free radical polymerization of the methyl acrylate substances of PFPE-DMA, resulting in the formation of a crosslinked network comprising a perfluorinated polymer.

[0102] In some embodiments, perfluorinated polymers with a higher degree of crosslinking are more resistant to degradation. This resistance can be determined, for example, by exposing the perfluorinated polymer to a solvent, such as a fluorinated solvent. The degree of crosslinking can be measured by any suitable method. In some cases, the degree of crosslinking can be measured directly, for example, by detecting the concentration of polymer crosslinks via spectroscopy. In other embodiments, the degree of crosslinking can be determined indirectly. For example, in some cases, the degree of crosslinking can be determined by measuring the degradation of the polymer in a solvent capable of dissolving the polymer when it is not crosslinked. Generally, polymers with a higher degree of crosslinking have lower solubility in a given solvent than polymers with a lower degree of crosslinking.

[0103] According to some embodiments, when a cross-linked polymer is immersed in a solvent capable of dissolving an uncross-linked polymer, the cross-linked polymer undergoes very little degradation. Any solvent capable of dissolving the polymer when it is uncross-linked can be used to determine the degree of cross-linking. According to some embodiments, fluorinated solvents can be used to determine the cross-linking of fluorinated polymers. For example, according to some embodiments, fluorinated solvents can be used to determine the cross-linking of perfluorinated polymers (e.g., perfluoropolyethers). In some embodiments, 1,3-bis(trifluoromethyl)benzene is a suitable solvent for determining the degree of cross-linking of polymers.

[0104] In some embodiments, the fluoropolymer has a high specific electrochemical impedance modulus as described above (e.g., at least 10). 6 The specific electrochemical impedance modulus (ohm-m) remains the same even after immersion in a solvent as described above. Similarly, in some embodiments, the fluoropolymer may have a low specific electrochemical impedance modulus reduction after immersion in a solvent, as previously described (e.g., a reduction in specific electrochemical impedance modulus of less than or equal to 50%).

[0105] Furthermore, in some embodiments, the perfluorinated polymer retains the high specific electrochemical impedance modulus (e.g., at least 10) even after immersion in a solvent as described above. 6 (The specific electrochemical impedance modulus of ohm-m). Similarly, in some embodiments, the perfluorinated polymer may have a low specific electrochemical impedance modulus reduction after immersion in a solvent, as previously described (e.g., a reduction in specific electrochemical impedance modulus of less than or equal to 50%).

[0106] According to some embodiments, the crosslinking of a polymer can be determined by measuring the specific electrochemical impedance modulus of the polymer after exposing it to a solvent capable of dissolving uncrosslinked polymers. For example, in some embodiments, more heavily crosslinked polymers retain a high specific electrochemical impedance modulus when the article is first formed and subsequently immersed in a fluorinated solvent (e.g., 1,3-bis(trifluoromethyl)benzene) for a period of time.

[0107] According to certain embodiments, the time for which the polymer is immersed in a solvent capable of dissolving the uncrosslinked polymer is greater than or equal to 5 seconds, greater than or equal to 6 seconds, greater than or equal to 7 seconds, greater than or equal to 8 seconds, greater than or equal to 9 seconds, greater than or equal to 10 seconds, greater than or equal to 15 seconds, greater than or equal to 20 seconds, greater than or equal to 30 seconds, greater than or equal to 45 seconds, greater than or equal to 60 seconds, greater than or equal to 90 seconds, or longer.

[0108] To measure the specific electrochemical impedance modulus of a polymer after immersing it in a solvent capable of dissolving the uncrosslinked polymer, according to certain embodiments, the polymer is first dried. The polymer can be dried by any suitable method. For example, the polymer can be dried in nitrogen, in air, or in a vacuum.

[0109] Impedance frequency measurement, specific electrochemical impedance modulus and / or reduction in specific electrochemical impedance modulus value, polymer thickness, polymer immersion time, drying method, and combinations of solvents capable of dissolving the polymer when it is not crosslinked are also possible. For example, according to some embodiments, when a polymer is formed into an article having a minimum size of at least 0.3 micrometers and immersed in 1,3-bis(trifluoromethyl)benzene for a time of greater than or equal to 9 seconds, dried in nitrogen, and measured at 1 kHz, it exhibits at least 10 6 The specific electrochemical impedance modulus of ohm-m. As another example, according to certain embodiments, when the polymer is formed into an article having a minimum size of at least 0.3 micrometers and a minimum size of less than or equal to 3.0 micrometers, and is immersed in 1,3-bis(trifluoromethyl)benzene for more than or equal to 30 seconds, dried in nitrogen, and measured at 1 kHz, it exhibits at least 10 6 ohm-m specific electrochemical impedance modulus.

[0110] In some embodiments, the molecular weight (e.g., weight-average molecular weight) of the polymer before crosslinking is less than or equal to 1000 kDa, 500 kDa, 200 kDa, 100 kDa, 50 kDa, 40 kDa, 30 kDa, 20 kDa, 15 kDa, 10 kDa, 8 kDa, 5 kDa, or less. In some embodiments, the weight-average molecular weight of the polymer is greater than or equal to 1 kDa, 2 kDa, 3 kDa, 4 kDa, 5 kDa, 8 kDa, 10 kDa, 15 kDa, 20 kDa, 30 kDa, 40 kDa, or greater. Combinations of these ranges are possible. For example, in some embodiments, the weight-average molecular weight of the polymer may be greater than or equal to 1 kDa and less than or equal to 8 kDa. In other embodiments, the weight-average molecular weight of the polymer may be greater than 20 kDa. The weight-average molecular weight of the polymer can be determined by any suitable method, such as gel permeation chromatography.

[0111] According to some embodiments, the polymer may be an elastomer. For example, in some embodiments, the polymer may exhibit a low elastic modulus. For example, according to some embodiments, the polymer has an elastic modulus of less than 10 MPa, less than 5 MPa, less than 2 MPa, less than 1 MPa, or lower. In some embodiments, the polymer may exhibit high elastic tensile deformation. For example, in some embodiments, the polymer may exhibit elastic tensile deformation equal to or greater than 20%, 30%, 50%, or 100% strain. In some embodiments, combinations of these mechanical properties are possible. For example, in some embodiments, the polymer has an elastic modulus of less than 1 MPa and may exhibit elastic tensile deformation equal to or greater than 20% strain. The elastic modulus and / or elastic tensile deformation can be determined by any suitable method. For example, the elastic modulus and elastic tensile deformation can be measured using a tensile testing machine.

[0112] Some aspects relate to methods for preparing articles comprising fluorinated polymers. In some embodiments, the fluorinated polymer is deposited on a substrate. Some aspects relate to methods for preparing articles comprising perfluorinated polymers. In some embodiments, a perfluorinated polymer (e.g., a perfluoropolyether) is deposited on a substrate. According to some embodiments, the substrate may provide mechanical support for the article. In some embodiments, for example, if the article overlaps with a portion of the circuitry of the substrate, the substrate may functionally interact with the article.

[0113] The substrate can include any suitable material. For example, the substrate can be a semiconductor substrate. Semiconductors can include any suitable material. According to some embodiments, the substrate can include silicon, germanium, gallium arsenide, or combinations thereof. Other substrates, such as semiconductor substrates, are also possible.

[0114] In some embodiments, the substrate is coated. In some embodiments, the coating on the substrate can act as a release layer. A release layer is a layer that can, for example, promote the separation of the article from the substrate through its degradation. In some embodiments, spacers are added to the substrate. The spacers can include, for example, photoresist. According to some embodiments, adding spacers to the substrate can advantageously protect the article. For example, according to some embodiments, the spacers on the substrate are used to protect the article from contact with a mask (e.g., a photo-aligner mask) or from contact with a nitrogen diffuser.

[0115] For example, in some embodiments, the substrate is coated with a photoresist. Examples of photoresists include epoxy-based photoresists, such as a mixture of bisphenol A phenolic varnish epoxy resin and triarylthionium / hexafluoroantimonate (SU-8 photoresist), and a mixture of diazonium quinone (DNQ) and phenol-formaldehyde resin (DNQ-Novolacs). In some embodiments, the substrate is coated with a metal (e.g., nickel).

[0116] Plasma can be used to treat polymers. For example, in some embodiments, plasma is applied to a fluorinated polymer to form a treated fluorinated polymer. In some embodiments, plasma is applied to a perfluorinated polymer to form a treated perfluorinated polymer. Any suitable plasma can be used. According to some embodiments, the plasma is or contains atoms that form an inert gas. For example, according to some embodiments, the plasma contains nitrogen. According to some embodiments, the plasma contains argon. Treatment of fluorinated polymers can advantageously prepare the surface of the fluorinated polymer for interaction with external materials. For example, according to some embodiments, treatment of fluorinated polymers can introduce reactive, charged, and / or polarized sites on the surface of the fluorinated polymer, which can form chemical or physical bonds with subsequently deposited materials. In some embodiments, treatment of perfluorinated polymers advantageously prepares the surface of the perfluorinated polymer for interaction with external materials. For example, according to some embodiments, treatment of perfluorinated polymers can introduce reactive, charged, and / or polarized sites on the surface of the perfluorinated polymer, which can form chemical or physical bonds with subsequently deposited materials.

[0117] In some embodiments, treating the perfluorinated polymer with plasma formed of an inert gas can advantageously remove oxygen from the treated perfluorinated polymer. This prevents oxygen from reacting with the treated surface, advantageously enhancing the ability of the perfluorinated polymer to adhere to other materials. More generally, in some embodiments, the fluorinated polymer can be treated in a manner that advantageously removes oxygen from the treated fluorinated polymer. This prevents oxygen from reacting with the treated surface, advantageously enhancing the ability of the fluorinated polymer to adhere to other materials. As a result, in some embodiments, articles of any thickness and / or multiple layers containing perfluorinated polymers can be manufactured. Similarly, in some embodiments, articles of any thickness and / or multiple layers containing fluorinated polymers can be manufactured. The manufacture of multilayer articles containing fluorinated polymers can provide significant advantages for the preparation of articles containing high-density electrodes. For example, as described in more detail elsewhere herein, the manufacture of additional electrode rows on a sensor can include additional layers of manufacturing apparatus.

[0118] After the formation of the treated fluorinated polymer, additional materials can be deposited onto the treated fluorinated polymer. In some embodiments, additional materials are deposited onto the treated perfluorinated polymer (e.g., perfluoropolyether) after the formation of the treated perfluorinated polymer. The deposited additional material can be a conductive material or other materials. For example, in some embodiments, the deposited additional material may include a metal or metal alloy. According to some embodiments, the ability to deposit conductive materials is advantageous because it can be used to manufacture parts of electronic circuits (e.g., sensors). For example, conductive materials can be used to manufacture electrodes.

[0119] In some embodiments, the additive material is a polymer. In some embodiments, the polymer is not a perfluorinated polymer. In some embodiments, the additive material is not a fluorinated polymer. In some embodiments, the additive material is a photoresist.

[0120] According to some embodiments, polymers can be deposited onto treated perfluorinated polymers via solution processing. More generally, polymers can be deposited onto treated fluorinated polymers via solution processing. Due to the hydrophobic nature of perfluorinated polymers, according to some embodiments, perfluorinated polymers do not swell in the presence of nonfluorinated solvents. Similarly, in some embodiments, fluorinated polymers may not swell in the presence of nonfluorinated solvents due to their hydrophobicity. Fluorinated polymers may undergo low volume swelling during solution processing of other materials. In some embodiments, perfluorinated polymers may undergo volume swelling of less than or equal to 5%, less than or equal to 2%, less than or equal to 1%, less than or equal to 0.5%, less than or equal to 0.2%, or less. For example, perfluorinated polymers may undergo volume swelling of less than or equal to 5%, less than or equal to 2%, less than or equal to 1%, less than or equal to 0.5%, less than or equal to 0.2%, or less. According to some embodiments, low volume swelling of perfluorinated polymers can advantageously maintain a pattern with high lateral resolution, although the pattern still comprises multiple chemically distinct polymers. More generally, fluorinated polymers can advantageously retain patterns with high lateral resolution; however, due to their low volume swelling, the pattern still contains multiple chemically distinct polymers.

[0121] The deposited additional material can be an additional fluorinated polymer (e.g., an additional layer of fluorinated polymer). This may result in a thicker fluorinated polymer layer. In some embodiments, the fluorinated polymer layer has a minimum size of at least 0.3 micrometers, at least 0.5 micrometers, at least 0.7 micrometers, or greater, exhibiting a high degree of cross-linking. In some embodiments, the minimum size of the fluorinated polymer layer is less than or equal to 3 micrometers, less than or equal to 2.5 micrometers, less than or equal to 2 micrometers, or less than or equal to 1 micrometer. Combinations of these ranges are possible. For example, according to some embodiments, the fluorinated polymer layer has a minimum size of at least 0.3 micrometers and less than or equal to 3 micrometers.

[0122] In some embodiments, the deposited additional material is an additional layer of perfluorinated polymer. In some embodiments, depositing an additional perfluorinated polymer layer can result in a thicker perfluorinated polymer layer. In some embodiments, the perfluorinated polymer layer has a minimum size of at least 0.3 micrometers, at least 0.5 micrometers, at least 0.7 micrometers, or greater, exhibiting a high degree of cross-linking. In some embodiments, the minimum size of the perfluorinated polymer layer is less than or equal to 3 micrometers, less than or equal to 2.5 micrometers, less than or equal to 2 micrometers, or less than or equal to 1 micrometer. Combinations of these ranges are possible. For example, according to some embodiments, the perfluorinated polymer layer has a minimum size of at least 0.3 micrometers and less than or equal to 3 micrometers.

[0123] Figure 3 An exemplary representation of the method is presented. First, a perfluorinated polymer 204 is deposited on a substrate 200, the substrate 200 including a semiconductor 201 coated with a release layer 202. Next, plasma is applied to the perfluorinated polymer 204 to form a treated perfluorinated polymer 206. After forming the treated perfluorinated polymer layer 204a, material 208 is deposited onto the treated perfluorinated polymer layer 204a. Of course, it should be understood that the same method can be performed on any of the various fluorinated polymers described above, and is not particularly limited to perfluorinated polymers.

[0124] Additionally, certain aspects of this disclosure relate to articles formed by methods such as those described herein. According to one aspect, for example, the article may comprise one or more layers formed, for example, as described above. For example, in some embodiments, the article comprises a first layer, a second layer, and a third layer. According to some embodiments, the first layer comprises a polymer. The first layer may comprise a fluoropolymer. For example, the first layer may comprise a perfluorinated polymer (e.g., perfluoropolyether). In some embodiments, the second layer is bonded to the first layer. In some embodiments, the third layer is bonded to the second layer. The third layer may comprise a fluoropolymer. The bonded layers may be directly bonded, or they may be separated by one or more intermediate layers connecting them.

[0125] On one hand, this disclosure relates to articles comprising a perfluorinated polymer (e.g., perfluoropolyether). In some embodiments, the article comprises a first layer comprising a perfluorinated polymer (e.g., perfluoropolyether). According to some embodiments, the article comprises a second layer bonded to the first layer. In some embodiments, the article comprises a third layer bonded to the second layer and comprising a perfluorinated polymer (e.g., perfluoropolyether). According to some embodiments, the article comprises one or more additional layers (e.g., on top of the third layer). These can be formed, for example, as discussed herein.

[0126] In another aspect, this disclosure relates to articles comprising fluoropolymers. In some embodiments, the article comprises a first layer comprising a fluoropolymer. According to some embodiments, the article comprises a second layer bonded to the first layer. In some embodiments, the article comprises a third layer bonded to the second layer and comprising a fluoropolymer. According to some embodiments, the article comprises one or more additional layers (e.g., on top of the third layer). These can be formed, for example, as discussed herein.

[0127] Some embodiments may also include one or more additional layers. For example, embodiments may include additional layers to facilitate adhesion between the first, second, and / or third layers; layers that alter the dielectric properties of the article; sensing layers; and / or layers that insulate the article (e.g., electrical, thermal, chemical, etc.). One or more additional layers may include intermediate layers, such as a layer between the first and second layers, and / or they may be outer layers, such as a layer deposited on top of the third layer.

[0128] According to some embodiments, the thickness of the first layer is greater than or equal to 50 nanometers, greater than or equal to 100 nanometers, greater than or equal to 200 nanometers, greater than or equal to 300 nanometers, greater than or equal to 400 nanometers, greater than or equal to 500 nanometers, or larger. According to some embodiments, the thickness of the first layer is less than or equal to 5000 nanometers, less than or equal to 4000 nanometers, less than or equal to 3000 nanometers, less than or equal to 2000 nanometers, less than or equal to 1000 nanometers, less than or equal to 500 nanometers, or smaller. Combinations of these ranges are possible. For example, according to some embodiments, the first layer has a thickness greater than or equal to 50 nanometers and less than or equal to 5000 nanometers. As another example, according to some embodiments, the first layer has a thickness greater than or equal to 300 nanometers and less than or equal to 2000 nanometers.

[0129] According to some embodiments, the thickness of the second layer is greater than or equal to 50 nanometers, greater than or equal to 100 nanometers, greater than or equal to 200 nanometers, greater than or equal to 300 nanometers, greater than or equal to 400 nanometers, greater than or equal to 500 nanometers, or larger. According to some embodiments, the thickness of the second layer is less than or equal to 5000 nanometers, less than or equal to 4000 nanometers, less than or equal to 3000 nanometers, less than or equal to 2000 nanometers, less than or equal to 1000 nanometers, less than or equal to 500 nanometers, or smaller. Combinations of these ranges are possible. For example, according to some embodiments, the second layer has a thickness greater than or equal to 50 nanometers and less than or equal to 5000 nanometers. As another example, according to some embodiments, the second layer has a thickness greater than or equal to 300 nanometers and less than or equal to 2000 nanometers.

[0130] According to some embodiments, the thickness of the third layer is greater than or equal to 50 nanometers, greater than or equal to 100 nanometers, greater than or equal to 200 nanometers, greater than or equal to 300 nanometers, greater than or equal to 400 nanometers, greater than or equal to 500 nanometers, or larger. According to some embodiments, the thickness of the third layer is less than or equal to 5000 nanometers, less than or equal to 4000 nanometers, less than or equal to 3000 nanometers, less than or equal to 2000 nanometers, less than or equal to 1000 nanometers, less than or equal to 500 nanometers, or smaller. Combinations of these ranges are possible. For example, according to some embodiments, the third layer has a thickness greater than or equal to 50 nanometers and less than or equal to 5000 nanometers. As another example, according to some embodiments, the third layer has a thickness greater than or equal to 300 nanometers and less than or equal to 2000 nanometers.

[0131] According to some embodiments, the overlap of the surface area of ​​the second layer with the first layer is greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 25%, greater than or equal to 50%, greater than or equal to 75%, greater than or equal to 90%, greater than or equal to 95%, greater than or equal to 99%, or more. According to some embodiments, the overlap of the surface area of ​​the second layer with the first layer is less than or equal to 100%, less than or equal to 95%, less than or equal to 90%, less than or equal to 75%, less than or equal to 50%, less than or equal to 25%, or less. Combinations of these ranges are possible. For example, according to some embodiments, the overlap of the surface area of ​​the second layer with the first layer is greater than or equal to 5% and less than or equal to 100%.

[0132] According to some embodiments, the overlap of the surface areas of the second and third layers is greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 25%, greater than or equal to 50%, greater than or equal to 75%, greater than or equal to 90%, greater than or equal to 95%, greater than or equal to 99%, or more. According to some embodiments, the overlap of the surface areas of the second and third layers is less than or equal to 100%, less than or equal to 95%, less than or equal to 90%, less than or equal to 75%, less than or equal to 50%, less than or equal to 25%, or less. Combinations of these ranges are possible. For example, according to some embodiments, the overlap of the surface areas of the second and third layers is greater than or equal to 5% and less than or equal to 100%.

[0133] In some implementations, two layers can be considered to overlap in a region if a ray perpendicular to the surface of one layer and pointing away from that layer would extend through the other layer. Overlapping layers do not need to be in direct contact with each other. They may be in direct contact with each other, or they may be separated (e.g., through one or more intermediate layers). Additionally, it should be understood that although one or more (or all) layers may be substantially planar and / or rectangular in various implementations, this is not necessarily a requirement.

[0134] According to some embodiments, a portion of the second layer does not overlap with the first and / or third layers. For example, according to some embodiments, a portion of the second layer is exposed (e.g., to form an electrode). According to some embodiments, a portion of the second layer is covered by an unfluorinated polymer. For example, according to some embodiments, a portion of the second layer (e.g., an electrode) may be covered by a conductive polymer layer (e.g., PEDOT:PSS).

[0135] While the articles described herein may comprise at least three layers, in some embodiments, the articles described herein may comprise one or more layers. For example, the articles described herein may comprise 1, 2, 3, 4, 5, 8, 10, 15, 20, 25 or more layers. In some embodiments, the articles described herein may comprise less than or equal to 100, less than or equal to 50, less than or equal to 25 or fewer articles. Combinations of these ranges are also possible. For example, the articles described herein may comprise more than or equal to 1 layer and less than or equal to 100 layers. In some embodiments, the articles comprise multiple polymer layers (e.g., fluoropolymer layers). As an example, the articles may comprise alternating conductive layers and polymer layers.

[0136] In some embodiments, the article comprises a conductive layer adjacent to multiple layers of the article (e.g., adjacent to a fluoropolymer layer of the article). For example, in some embodiments, the article includes an electrode. The electrode may be a surface electrode of the article. The article may include multiple electrodes (e.g., multiple surface electrodes). In some embodiments, the article includes a substrate (e.g., a substrate designed for implantation within a subject). The substrate may include multiple electrodes. According to some embodiments, as described above, electrodes can be formed on the article by depositing material onto a treated fluoropolymer of the article. For example, as described above, electrodes can be formed by depositing a metal layer on top of a treated fluoropolymer layer. In some embodiments, the electrode may be electrically connected to a conductive layer of the article. For example, the electrode may contact a metal layer of the article such that the electrode can be electrically connected to an external circuit.

[0137] The article can be used to determine electrical activity using multiple electrodes on a substrate of the article, which is at least partially contained within a subject. In some embodiments, the electrodes can be used to determine electrical activity. For example, multiple electrodes can be used to determine electrical activity. Electrical activity can be neural activity. For example, the electrodes can be used to determine the electrical activity of a single cell within a subject (e.g., a living subject). For example, the cell can be a neuron. The electrodes can be configured to contact the cell for a period of time. For example, in some embodiments, the electrodes are configured to contact the cell for a period of time greater than or equal to 1 day, greater than or equal to 5 days, greater than or equal to 7 days, greater than or equal to 14 days, greater than or equal to 3 weeks, greater than or equal to 4 weeks, or longer. In some embodiments, the electrodes are configured to contact the cell for a period of time less than or equal to 6 months, less than or equal to 3 months, less than or equal to 6 weeks, less than or equal to 5 weeks, less than or equal to 4 weeks, less than or equal to 14 days, or shorter. Combinations of these ranges are possible. For example, in some embodiments, the electrodes are configured to contact the cell for a period of time greater than or equal to 1 day and less than or equal to 6 months. In some embodiments, the electrodes are configured to continuously monitor electrical activity from the vicinity of the cell over a period of time (e.g., at least 5 days). In some implementations, the electrodes are configured to intermittently monitor electrical activity from the vicinity of the cell over a period of time.

[0138] In some embodiments, electrodes can be used to electrically stimulate cells. For example, multiple electrodes can be used to stimulate cells. Electrodes can be used to stimulate neural activity. For example, electrodes can be used to stimulate the electrical activity of neurons in a subject (e.g., a live subject). In some embodiments, electrodes can be used to stimulate neurons near a brain probe.

[0139] The article may include electrodes having an electrode number density. The electrode number density can be the area density of electrodes located on an implantation portion of the article (e.g., the substrate of the article). In some embodiments, the electrodes have a number density greater than or equal to 10. -5 Electrodes / micrometer 2 10 or greater -4 Electrodes / micrometer 2 10 or greater -3 Electrodes / micrometer 2 10 or greater -2 Electrodes / micrometer 2 10 or greater -1 Electrodes / micrometer 2 Or a higher electrode number density. In some embodiments, the electrodes have a number density of less than or equal to 10. 1 Electrodes / micrometer 2 Less than or equal to 10 0 Electrodes / micrometer 2 Less than or equal to 10 -1 Electrodes / micrometer2 Or even smaller electrode number densities. Combinations of these ranges are possible. For example, in some embodiments, the electrodes have a number density greater than or equal to 10. -5 Electrodes / micrometer 2 and less than or equal to 10 1 Electrodes / micrometer 2 Electrode number density.

[0140] In some embodiments, the article of manufacture may be patterned (e.g., by means of a mask), as described in more detail below. The article of manufacture may have a resolution (e.g., spatial resolution). In some cases, the resolution may be determined as the lateral resolution. One advantage of certain articles of manufacture described herein is their high lateral resolution. For example, in some embodiments, the article of manufacture has a lateral resolution of 30 micrometers or less, 20 micrometers or less, 10 micrometers or less, 5 micrometers or less, 2 micrometers or less. The lateral resolution of a structure can be determined by any suitable technique, such as scanning electron microscopy.

[0141] In some embodiments, the article is located on a substrate (e.g., a semiconductor substrate). In some embodiments, the article is not on the substrate, for example, because it has been separated from the substrate. According to some embodiments, the substrate includes (e.g., coated with) a release layer as described above. In some embodiments, preparing the article on a substrate containing a release layer facilitates the separation of the article from the photoresist.

[0142] Perfluoropolyethers can have any suitable molecular weight. According to some embodiments, it may be advantageous for the perfluoropolymer (e.g., perfluoropolyether) to have a low molecular weight (e.g., a weight-average molecular weight of less than 8 kDa, or other molecular weights, such as those described herein). In some embodiments, the low molecular weight of the perfluoropolymer ensures that the perfluoropolyether remains rigid when crosslinked on a substrate, thereby producing a rigid perfluoropolyether.

[0143] According to some embodiments, a high molecular weight (e.g., a weight-average molecular weight greater than or equal to 20 kDa) may be advantageous for perfluorinated polymers. According to some embodiments, the high molecular weight of perfluorinated polymers can provide them with advantageous physical properties for sensing applications. For example, according to some embodiments, the high molecular weight of perfluorinated polymers can mean that the perfluorinated polymer is an elastomer.

[0144] In some embodiments, the second layer comprises a conductive material. This may be advantageous in some embodiments, for example, when the article is part of a device as described below, because it allows the article to be electronically connected to the device. According to some embodiments, this may also allow the article to act as a sensor of such a device, since electrical signals received by a portion of the article can be conducted through the article to the device. In some embodiments, the second layer comprises a metal or metal alloy, such as aluminum, silver, copper, gold, etc. The second layer can be deposited by any suitable method. For example, the second layer can be deposited by vapor deposition (e.g., physical vapor deposition, chemical vapor deposition). According to some embodiments, the second layer may be electrically connected to an electrode (e.g., a working electrode).

[0145] The articles described herein may have suitable mechanical properties. For example, in some embodiments, the electrodes have a mechanical property greater than or equal to 10. 3 Pa, greater than or equal to 10 4 Pa, greater than or equal to 10 5 Pa, greater than or equal to 10 6 A total elastic modulus of Pa or greater. In some embodiments, the electrode has a total elastic modulus of less than or equal to 10 Pa. 9 Pa, less than or equal to 10 8 Pa, less than or equal to 10 7 Pa, less than or equal to 10 6 A total elastic modulus of Pa or less is possible. Combinations of these ranges are possible. For example, in some embodiments, the electrode has a total elastic modulus greater than or equal to 10 Pa. 3 Pa and less than or equal to 10 9 Total elastic modulus Pa.

[0146] In some embodiments, the article includes a substrate having an electrode number density to total elastic modulus ratio greater than or equal to 10. -11 Electrodes / micrometer 2 -Pa, greater than or equal to 10 -10 Electrodes / micrometer 2 -Pa, greater than or equal to 10 -9 Electrodes / micrometer 2 -Pa, greater than or equal to 10 -8 Electrodes / micrometer 2 -Pa, or greater. In some embodiments, the article comprises a substrate having an electrode number density to total elastic modulus ratio of less than or equal to 10. -6 Electrodes / micrometer 2 -Pa, less than or equal to 10 -7 Electrodes / micrometer 2 -Pa, less than or equal to 10 -8 Electrodes / micrometer 2-Pa, less than or equal to 10 -9 Electrodes / micrometer 2 Pa or less. Combinations of these ranges are possible. For example, in some embodiments, the article comprises a substrate having an electrode number density to total elastic modulus ratio greater than or equal to 10. -11 Electrodes / micrometer 2 -Pa and less than or equal to 10 -6 Electrodes / micrometer 2 -Pa.

[0147] Another aspect of this disclosure relates to various devices. In some embodiments, these devices can be exposed to physiological conditions. For example, in some embodiments, these devices can be implanted into a subject. According to some embodiments, the device includes electronic circuitry. In some embodiments, an article of writing covers at least a portion of the electronic circuitry of the device. For example, according to some embodiments, electrodes of the article of writing cover electrodes of the electronic circuitry. According to some embodiments, the article of writing and the electronic circuitry communicate electronically. In some cases, the electronic circuitry can be configured to receive signals (e.g., electronic signals) from the article of writing. In some cases, the electronic circuitry can be configured to amplify signals from the article of writing; for example, according to some embodiments, the article of writing can be used as a sensor (e.g., a sensor of neural activity).

[0148] In some embodiments, the method includes applying light to a substrate. For example, according to some embodiments, light may be applied to a substrate comprising a photoresist. According to some embodiments, light is applied via a mask. In some cases, the mask defines a pattern. For example, in some embodiments, the mask defines a light pattern on the substrate. The method may include aligning and patterning a fluoropolymer (e.g., a perfluorinated polymer). According to some embodiments, the method may include aligning and patterning a perfluoropolyether. The fluoropolymer may be aligned relative to the mask. For example, according to some embodiments, the perfluoropolyether is aligned relative to a mask (e.g., a photo-aligner mask). According to some embodiments, alignment includes moving the mask relative to the substrate. In some embodiments, a photoresist spacer is deposited on a substrate containing the polymer, as described above. According to some embodiments, the addition of the spacer may allow the mask to contact the spacer without contacting the polymer. Advantageously, according to some embodiments, the addition of the spacer may prevent the mask from damaging the polymer during alignment. In some embodiments, material is deposited onto the substrate and / or photoresist based on a pattern of the mask. For example, the material may be a metal. In some implementations, a portion of the photoresist is removed to create a substrate patterned with the deposited material.

[0149] In some embodiments, the pattern has a lateral resolution. For example, in some embodiments, the pattern has a lateral resolution of 30 micrometers or less, 20 micrometers or less, 10 micrometers or less, 5 micrometers or less, 2 micrometers or less, or lower.

[0150] According to some embodiments, the light has an average wavelength. In some embodiments, the average wavelength of the light is less than or equal to 1500 nm, less than or equal to 1000 nm, less than or equal to 800 nm, less than or equal to 750 nm, less than or equal to 600 nm, or smaller. In some embodiments, the average wavelength of the light is greater than or equal to 100 nm, greater than or equal to 200 nm, greater than or equal to 300 nm, or larger. Combinations of these ranges are possible. For example, according to some embodiments, the average wavelength of the light is greater than or equal to 100 nm and less than or equal to 1500 nm.

[0151] In some embodiments, at least a portion of the article of manufacture (e.g., a sensor, substrate, etc.) is implanted into the subject's body. For example, part or all of the article of manufacture may be implanted into the subject's body. The article of manufacture may be implanted at a location within the subject. For example, the article of manufacture may be implanted in the brain. In some embodiments, the article of manufacture is configured to reside permanently within the subject's body. For example, the article of manufacture may be configured to reside permanently within an organ of the subject. For example, the article of manufacture may be configured to reside permanently within the subject's brain. In some embodiments, the article of manufacture may be a brain probe or a neural sensor.

[0152] For all purposes, the following applications are incorporated herein by reference in their entirety: U.S. Provisional Application No. 63 / 159,623, entitled “Perfluorinated Elastomers for Brain Probes and Other Applications,” filed March 11, 2021; and U.S. Provisional Application No. 63 / 290,732, entitled “Fluorinated Elastomers for Brain Probes and Other Applications,” filed December 17, 2021.

[0153] The following examples are intended to illustrate certain embodiments of the present invention, but do not represent the full scope of the invention.

[0154] Example 1

[0155] This embodiment describes the fabrication of metal interconnects on the surface of a perfluoropolyether layer. In this embodiment, the perfluoropolyether is perfluoropolyether dimethacrylate (PFPE-DMA), which is an elastomer. First, a layer of PFPE-DMA is prepared on a substrate. Then, a photoresist is deposited on the PFPE-DMA layer. Using a nitrogen chamber and a mask aligner, the photoresist is photodegraded to form a surface pattern, exposing the patterned portion of the PFPE-DMA layer. The lateral resolution of the patterned portion of the PFPE-DMA is less than 5 micrometers. The patterned portion of the PFPE-DMA is exposed to argon plasma to form treated PFPE-DMA, and an aluminum adhesion layer is sputtered onto the exposed surface. Next, gold is deposited onto the aluminum, forming a layer of gold interconnects and electrodes on top of the patterned portion of the PFPE-DMA layer. Finally, excess metal is removed by a stripping method. In this embodiment, the remaining photoresist is photodegraded to remove excess metal deposited on the photoresist. The result is a patterned gold circuit portion, including gold interconnects and electrodes, deposited on the surface of the PFPE-DMA layer with a lateral resolution of less than 5 micrometers.

[0156] In some cases, a second argon plasma exposure is used without a mask to allow the deposition of additional layers. For example, in one case, a PFPE-DMA layer is deposited on top of a circuit, forming a third layer encapsulating conductive layers. In other cases, a first argon plasma exposure can be used without a mask to deposit a PFPE-DMA layer on top of a previously deposited PFPE-DMA layer. By repeating this process, PFPE-DMA layers with a thickness exceeding 300 nanometers can be fabricated. This, in turn, allows the fabrication of electronic devices on PFPE-DMA layers with a thickness exceeding 300 nanometers. By repeating this method, multilayer packaged circuits can be fabricated within the PFPE-DMA layer.

[0157] These results demonstrate the ability to manufacture multilayer articles containing a perfluoropolyether layer. In particular, these results indicate that such multilayer articles can be used to manufacture circuits containing gold electrodes and gold interconnects encapsulated within PFPE-DMA.

[0158] Example 2

[0159] In some cases, deposited perfluoropolyether layers can exhibit high specific electrochemical impedance modulus after prolonged exposure to saline solutions. This example compares the decrease in specific electrochemical impedance modulus of the polymer measured after prolonged immersion in 1x or 10x phosphate buffer solutions at 37°C or 70°C. Perfluoropolyether layers such as PFPE-DMA are compared with layers of polydimethylsiloxane (PDMS), styrene-ethylene-butene-styrene (H-SEBS), polyimide (PI), and SU-82000.5 epoxy photoresist (used as comparatives in this example).

[0160] Electrochemical impedance spectroscopy was performed in a phosphate buffer solution using a standard three-electrode setup. Figure 2 The setup for a three-electrode electrochemical impedance spectroscopy (TEIS) measurement is shown. In these experiments, a working electrode (gold) 122 is connected to a conductor 108 deposited on a substrate 124 and encapsulated within a dielectric layer 126 comprising one of the polymers. Two other electrodes, a counter electrode 110 (platinum) and a reference electrode 112 (silver / silver chloride), are connected to the other side of the dielectric layer, allowing the use of electrodes from... Electrochemical impedance spectroscopy was performed using an SP-150 potentiostat and its commercial software (EC-lab). Experiments were conducted in buffer solution 114. This technique provides an estimate of ion diffusion rate based on the time required to observe the impedance decrease, and an estimate of ionic conductivity based on the obtained Nyquist plot.

[0161] For each measurement, three frequency scans were performed from 1 MHz to 0.1 Hz. A sinusoidal voltage of 100 mV was applied between peaks. Measurements were taken at logarithmic intervals every decade. For each data point, the response to 10 consecutive sinusoidal curves (intervals of 10% of the period duration) was accumulated and averaged. The thickness H of each layer was determined as a fraction of micrometers (e.g., a 3-micrometer thick sample was represented by H = 3.0). All thickness measurements were performed using a Bruker Dektak Xt Stylus profilometer. The applied force was set to 1 mg, and the scan rate was set to 0.67 micrometers per second. Two-point surface leveling was performed using the tool's commercial software.

[0162] The polymer layer was immersed in 10x phosphate buffered solution (PBS) under rapid aging conditions at 70°C. Figure 4A The specific electrochemical impedance modulus (top) and phase (bottom) of dielectric polymers under pristine conditions and after aging in 10xPBS at 70 °C were plotted (for PFPE, SU-8, H-SEBS, PI, t / H). 2 =5 days / micrometer 2 and for PDMS t / H 2 = 1.55 days / micrometer 2 ). Figure 4B and 4C The immersion layer, measured at 1 kHz and 1 Hz, is presented as a function of time (via H). 2The specific electrochemical impedance modulus (SEM) was normalized. Under rapid aging conditions, the SEM of all polymers experienced a decrease. However, compared to the SEM of other polymers, the SEM of the PFPE-DMA layer was very similar to that of the SU-8 layer, and the decrease was very slow. These data demonstrate the long-term stability of the perfluoropolyether layer under physiological saline conditions. Figure 4D Similar to Figure 4B However, it added electrochemical impedance spectroscopy measurements of the PFPE-DMA layer recorded under physiological conditions (37°C, 1xPBS). This visualization demonstrates the stability of the PFPE-DMA layer over 250 days under physiological conditions.

[0163] These results were further validated by conductivity measurements. In these measurements, large areas (ranging from 150 to 300 cm²) were prepared on glass slides according to the protocol used to prepare films for electrochemical impedance measurements. 2 The dielectric film was first prepared and then immersed in deionized water to promote its peeling. After peeling, the wrinkled film was transferred to a glass bottle for the remaining experiments. The wrinkled film was first soaked in deionized water at ambient temperature for 3 weeks, and replaced periodically to remove any impurities that might affect the ionic conductivity. A conductivity meter (with calibration function) was used. A pocket conductivity meter was used to confirm that the conductivity of the surrounding solution remained negligible after 3 weeks, thus ensuring the cleaning process was complete. The two electrodes of the conductivity meter had an area of ​​1 cm². 2 The electrode spacing is 1 cm. The sensor resolution is 1 micro Siemens, and the temperature dependence of conductivity in the range of -5 to 50°C is automatically compensated to provide the value at 25°C.

[0164] The samples were transferred to new glass vials containing a large volume of 10xPBS solution for complete ion immersion and placed at a fixed temperature (4°C, 37°C, or 65°C) for 3 weeks. This was subsequently confirmed to be a long time compared to the characteristic diffusion time of ions in the material. After equilibration in the biofluid, the samples were thoroughly rinsed twice consecutively in deionized water (30 seconds each time) to remove surface ions, then dried at 65°C for 30 minutes, and mass measurements were collected.

[0165] Next, the samples were transferred to new glass vials containing 4.00 mL of deionized water and stored at a fixed temperature (4°C, 37°C, or 65°C). A conductivity cell was used to monitor temperature and conductivity. The conductivity of the deionized water solution was measured periodically to determine the amount of ions desorbed from each material over time. This procedure is illustrated in [illustration]. Figure 5A In the presence of a conductivity meter, it was shown that the perfluoropolyether was equilibrated in deionized (DI) water, then absorbed ions when it was equilibrated in 10x phosphate buffer solution, and then emitted ions when it was equilibrated again in DI water. Figure 5B The boundary conditions and the diffusion distribution resulting from these conditions are shown, along with the evolution of the concentration distribution at different time points. Changes in conductivity can determine the ion concentrations desorbed over time for each dielectric polymer at different temperatures. Figure 5C The results of these experiments are presented, showing the ion concentration of each polymer in initial deionized water as a function of time at 4°C, 37°C, and 65°C (via H₂). 2 standardization).

[0166] The plateau period of concentration is proportional to the ionic solubility S of the polymer, and the theoretical solution of the corresponding diffusion one-dimensional boundary problem is fitted to the experimental data to obtain the ionic diffusivity D. Figure 5D The experimental results and theoretical fits for each polymer at 37°C are shown. Then, using... Figure 6 Equation (1) shown in the figure determines the ionic conductivity.

[0167]

[0168] Where σ(sigma) is the ionic conductivity, q is the unit charge, k is the Boltzmann constant, T is the temperature, D is the ion diffusivity, S is the ion solubility, and C is the ionic conductivity. out This refers to the ion concentration in the surrounding biological fluid at equilibrium. The ionic conductivity determined by electrochemical impedance spectroscopy (Method #1) is compared with the ionic conductivity determined by conductivity spectroscopy (Method #2). Figure 5E The comparisons showed good consistency. The two methods were consistent in both overall trends and magnitudes. Based on these two measurements, PFPE-DMA stands out from other dielectric elastomers due to its low ionic conductivity resulting from its low ionic diffusivity (Table 2).

[0169] Table 1. Ionic conductivity, diffusivity, and solubility of dielectric polymers obtained by conductivity.

[0170]

[0171]

[0172] To further understand the properties of low ionic conductivity in PFPE-DMA, conductivity was measured at different temperatures to determine the average diffusion activation energy and heat of solution of ions in the range of 4℃–65℃ using the Arrhenius relation. Figures 7A-7C The ion diffusion rate D( is the measured value for each polymer) Figure 7A ), Ion solubility S ( Figure 7B ) and ion permeability P ( Figure 7C The Arrhenius plot of ) is shown. The energy parameters in Table 2 were obtained using linear fitting. In terms of diffusion rate and solubility trends, PFPE-DMA is closer to SU-8 than other elastomers.

[0173] Table 2. Average activation energy E of ion diffusion rate calculated according to the Arrhenius model a The heat of solution H of ionic solubility s .

[0174] Material PDMS H-SEBS PFPE SU8 <![CDATA[E a (kJ / mol)]]> 10.32 4.56 13.25 9.02 <![CDATA[H s (kJ / mol)]]> 3.03 1.04 11.83 14.35

[0175] Example 3

[0176] This embodiment demonstrates a method for characterizing the crosslinking of perfluoropolyether layers using specific electrochemical impedance spectroscopy (PIS). For this purpose, a perfluoropolyether deposited layer (PFPE-DMA in this embodiment) with a thickness of H (as described in Example 2) is immersed in 1,3-bis(trifluoromethyl)benzene for 30 seconds / H. 2 During the specified time period, the sample was gently stirred to remove uncrosslinked polymer chains. Next, the sample was dried using a nitrogen stream. Finally, the sample was immersed in a 1x phosphate buffer solution, and its electrochemical impedance was measured according to the protocol of Example 2. Generally, membranes known to have a higher degree of crosslinking were observed to have significantly higher specific electrochemical impedance modulus, demonstrating that specific electrochemical impedance modulus can be used as an indirect test of crosslinking in these membranes.

[0177] Example 4

[0178] This example describes the preparation of a perfluoropolyether dimethacrylate (PFPE-DMA) photolithography precursor. Unless otherwise stated, all chemicals were derived from Sigma-Aldrich and were ready for use without further purification. All volume fractions described correspond to volumes of 1,1,1,3,3-pentafluorobutane.

[0179] First, 0.8 g / mL PFPE diol was dissolved in 1,1,1,3,3-pentafluorobutane (Alfa Aesar, H33737). The solution was mixed for 3 hours. Then, 22 mg / mL isophorone diisocyanate (IPDI, 317624) and 0.8 mg / mL dibutyltin diacetate (DBTDA, 290890) were added to the solution, and the reaction was carried out under nitrogen for 48 hours. The product could be viscous or solid. Then, 30 mg / mL ethyl 2-isocyanate methacrylate (IEM, 477060) and 0.8 mg / mL DBTDA were added to the product, and the reaction was carried out further under nitrogen at room temperature for 48 hours. The final product solution was filtered through a 0.2-micron glass fiber syringe filter to obtain a clear and colorless oil. The IPDI solvent in the oil was removed by rotary evaporation to obtain pure PFPE-DMA. Finally, 0.5-1.5 g / mL PFPE-DMA and 1 wt% photoinitiator bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (511447) were dissolved in bis(trifluoromethyl)benzene (251186) to obtain the precursor.

[0180] Example 5

[0181] This embodiment illustrates an exemplary method for manufacturing certain articles containing perfluoropolyethers. In a more specific embodiment, this method is used to manufacture PFPE-DMA-encapsulated brain probes. Figure 8 A schematic diagram of this exemplary method is presented. Unless otherwise stated, all photoresists and developers are available from MicroChem Corporation.

[0182] 1. Device fabrication begins with the preparation of the Ni sacrificial layer. Figure 8 Step 1). A 3-inch thermally oxidized silicon wafer (2005, University wafer) was rinsed with acetone, rinsed with isopropanol (IPA), rinsed with water, and dried. Then, the 3-inch thermally oxidized silicon wafer was baked at 110°C for 3 minutes and treated with oxygen (O2) plasma at 100W, 40 standard cubic centimeters per minute (sccm) for 30 seconds. Hexamethyldisilazane, LOR 3A photoresist, and S1805 photoresist layers were spin-coated onto the wafer at 4000 rpm for 1 minute. After LOR 3A photoresist deposition, it was hard-baked at 180°C for 5 minutes. Subsequently, S1805 photoresist was applied and hard-baked at 115°C for 1 minute. The photoresist was then heated at 40 mJ / cm². 2 Expose under UV light and develop with CD26 developer for 50 seconds, rinse with DI water and blow dry. Then, a 100 nm nickel layer is thermally deposited on the wafer and stripped for 3 hours in Remover PG solvent stripper based on N-methyl-2-pyrrolidone (NMP).

[0183] 2. Next, a negative photoresist was used to fabricate the spacers. SU-8 2010 epoxy photoresist was spin-coated onto the wafer at 3000 rpm for 2 minutes, pre-baked at 60°C for 2 minutes, and then pre-baked at 95°C for 4 minutes. The SU-8 2010 epoxy photoresist was applied at 200 mJ / cm². 2 Expose to UV light, then bake at 60°C for 2 minutes and at 95°C for 2 minutes and 30 seconds. Finally, develop SU-8 2010 epoxy photoresist in SU-8 developer (1-methoxy-2-propanol acetate) for 2 minutes, rinse with IPA and dry.

[0184] 3. Fabrication of the bottom PFPE-DMA layer ( Figure 8 (Step 3). First, the wafer is cleaned with acetone, IPA, and water and then dried. Then, the PFPE-DMA precursor described in Example 4 is spin-coated onto the wafer at 2000-6000 rpm for 1 minute, followed by pre-baking at 95°C for 1 minute to obtain a thickness of 500 nm to 3 μm, depending on the spin speed and precursor concentration. Using an exemplary custom nitrogen diffuser, the PFPE-DMA is aligned in a photomask aligner and 20 mJ / cm² is applied. 2 UV patterning. Figure 9A A schematic diagram of an exemplary nitrogen diffuser is presented, and Figure 9B An image of an exemplary nitrogen diffuser set on a Karl Suss MA6 mask aligner is presented. The PFPE was then baked at 95°C for 1 minute, developed in a developer solution (bis(trifluoromethyl)benzene:1,1,1,3,3-pentafluorobutane = 1:3) for 1 minute, and blow-dried. The PFPE pattern was then hard-baked at 150°C for 50 minutes.

[0185] 4. Create a metallic trace on top of the bottom PFPE-DMA ( Figure 8 (Step 4). First, the bottom PFPE is surface-treated with argon plasma at 20-30W and 40sccm argon gas for 2-6 minutes.

[0186] 5. As described in step 1, pattern the positive photoresist LOR 3A and S1805 or S1813 on the wafer to prepare a sacrificial layer. Then, treat the surface again with argon plasma (20-30W, 40 sccm argon, 2-6 minutes), followed by sequential deposition of aluminum-gold, aluminum-gold-aluminum, aluminum-gold-platinum, chromium-gold, or chromium-gold-chromium metal layers by sputtering, each layer having a thickness in the range of 20-100 nm. Finally, strip the metal layers overnight in Remover PG. Figure 8 (Step 5).

[0187] 6. Deposit the subsequent PFPE-DMA layer according to the method described in step 3. Figure 8 (Step 6).

[0188] 7. Steps 4 to 6 can be repeated multiple times to obtain the required number of metal electrode layers, which are then fully encapsulated by a perfluorinated elastomer.

[0189] 8. A negative photoresist is used to fabricate a microfabricated plastic framework that holds a perfluorinated elastomer-encapsulated brain probe flat during release. One method uses SU-8 2010 spacers ( Figure 8 Step 2), as described herein. SU-8 2010 was spin-coated onto the wafer at 3000 rpm for 2 minutes, pre-baked at 60°C for 2 minutes, and then pre-baked at 95°C for 4 minutes. SU-8 was applied with 200 mJ / cm². 2 The sample was exposed to UV light, then baked at 60°C for 2 minutes, followed by baking at 95°C for 2 minutes and 30 seconds. Finally, the SU-8 2010 was developed in SU-8 developer for 2 minutes, rinsed with IPA, and dried. Depending on the final thickness required for the microfabrication of the plastic frame, which must be thicker than the total thickness of the brain probe, different SU-8 chips can be used. This manufacturing process has been successfully applied to SU-8 2010, SU-8 2025, and SU-8 2050.

[0190] 9. In some embodiments, a low electrochemical impedance material is deposited on the tip of the electrode using a platinum, aluminum-platinum, or chromium-platinum layer with a thickness in the range of 20-80 nanometers, instead of the metal, following a process similar to steps 4-5. The SP-150 potentiostat and its commercial software (EC-lab) are used for voltage or current control during electrodeposition. The electrode from the device is connected to the working electrode. The counter electrode is a platinum wire, which also serves as a voltage reference, and is immersed in the precursor solution. For platinum black, the precursor is a 0.8 wt% chloroplatinic acid solution, and the applied current is -1 mA / cm². 2 The reaction lasted 5-10 minutes. For PEDOT-PSS deposition, an electrolyte consisting of an aqueous solution of 0.01 M 3,4-ethylenedioxythiophene (EDOT) (Sigma-Aldrich, USA) and 0.1 M sodium PSS (Sigma-Aldrich, USA) was used. The electrochemical polymerization reaction was carried out under constant voltage conditions. In constant voltage mode, polymerization was carried out at a constant current of 1 V for 30 seconds.

[0191] Example 6

[0192] This example demonstrates the properties of a product containing PFPE-DMA. Long-term immersion experiments under physiological conditions (1x phosphate buffer solution, 37°C) were used to compare the electrochemical impedance spectroscopy (EIS) stability of PFPE-DMA and SU-8. The results of these EIS measurements are presented in… Figure 10A In the middle. After more than 15 months (more than 450 days), PFPE-DMA maintained a high specific electrochemical impedance modulus, sufficient to electrically insulate the brain probe, and comparable to that of SU-8. However, SU-8 is a rigid polymer with an elastic modulus of approximately 2 gigapascals, while PFPE-DMA, according to some embodiments, is an elastomer with an elastic modulus of only 0.50 megapascals, more than 4000 times softer. Stress-tension profiles of the samples were obtained under uniaxial tension in a pure shear test geometry using an Instron instrument. Figure 10B The stress-tension curves for each polymer are presented. Figure 10C The elastic modulus (E) of various polymers was compared with the normalized half-life (t) of their specific electrochemical impedance modulus at 1 kHz. 1 / 2 / H 2 (This is a comparison of the soaking time required to reduce the initial specific electrochemical impedance modulus by 50%), and perfluoropolyether elastomers are the only materials with a high normalized half-life. 1 / 2 / H 2 The definite graphical representation in Figure 4B As shown in the image.

[0193] Example 7

[0194] This embodiment demonstrates the nanofabrication of a brain probe containing a perfluoropolyether elastomer and shows that PFPE-DMA does not swell when immersed in organic solutions commonly used in photolithography, maintaining nanoscale smoothness.

[0195] The PFPE-DMA was photopatterned using the exemplary custom nitrogen diffuser described in Example 4 to generate an inert atmosphere during UV exposure, thereby achieving nanoscale photopatterning. To maintain the nanoscale smoothness of the PFPE-DMA, negative photoresist spacers were patterned on the wafer to prevent direct contact between the non-crosslinked PFPE-DMA precursor and the photomask. Finally, the exposed surfaces of the PFPE-DMA were treated with inert gas plasma (e.g., nitrogen, argon, etc.) to enhance the adhesion of metals and other subsequently deposited materials to the PFPE-DMA.

[0196] Figure 11A An exemplary device produced using this method is shown, in which three layers of PFPE-DMA sandwich two layers of metal interconnects. This manufacturing workflow is compatible with wafer-level fabrication, and... Figure 11B An exemplary device is presented, manufactured on a 3-inch wafer (7.62 cm). Figure 11C Bright-field optical imaging was presented, highlighting the high quality of the PFPE-DMA and the metallic lines, patterned in an alternating sequence. Figure 11D Scanning electron microscope (SEM) images are presented, revealing a uniform pattern throughout the device, while Figure 11E A focused ion beam (FIB) cross-sectional image is presented, showing (i) no delamination from the PFPE-DMA layer and (ii) a sputtered metal interconnect tightly bonded to the PFPE-DMA layer. The conductivity of the metal electrode is quantitatively verified by measuring its resistance as a function of its aspect ratio. Figure 12A The experimentally observed dependence of resistance R on aspect ratio is presented. For a typical aluminum / gold (40 nm / 100 nm) interconnect, a conductivity of 2.25 ± 0.55 10 is observed. 7 S / m, this result is comparable to the conductivity predicted using standard values. The electrode array was released from the fabrication substrate and a 2% uniaxial strain was applied. Figure 12B As shown, no change in the resistance of the interconnect was observed after applying uniaxial strain. According to some embodiments, the electrode tips are coated with PEDOT:PSS or platinum black using standard electroplating techniques. Figures 13A-13B The specific electrochemical impedance modulus as a function of frequency was presented for electrodes with and without a PEDOT:PSS coating. Figure 13A ) and phase ( Figure 13B ).

[0197] Example 8

[0198] This embodiment demonstrates the successful implantation of a brain probe comprising a perfluorinated elastomer. The brain probe was synthesized as described above. Figure 14 A photograph of a microfabricated plastic frame is shown, which is used to keep the device flat during release from the substrate. The microfabricated plastic frame was manufactured as described in Example 5. Next, the microfabricated plastic frame was removed prior to implantation. A 70-micrometer diameter, tip-etched tungsten shuttle was used to guide the perfluorinated elastomer brain probe into the mouse brain tissue. Figure 15A This is a photograph showing a perfluorinated elastomer-based brain probe implanted into mouse brain tissue according to one embodiment. The spindle is then removed, leaving the device within the mouse's brain tissue. Figure 15B The image shows a freely moving mouse with a brain probe based on perfluorinated elastomer implanted in each hemisphere of its brain.

[0199] A flat, flexible cable connected at one end to the device is connected to a voltage amplifier to record electrophysiological data. Measurements are taken at different sites on the device from freely moving mice (e.g., Figure 15B The neural activity of mice. Blackrock The Cereplex μ probe is attached to a flat, flexible cable in the mouse's head. TM The Direct data acquisition card and Cereplex software are used to record and filter electrophysiological recordings. Figure 16A An exemplary location of the device is shown, and bursts of activity on multiple electrodes recorded 3 days after implantation are illustrated by filtered signals (bandpass filter 300-6000Hz). Figure 16B Presentation Figure 16A A magnified view of the framed area, and Figure 16C Presented Figure 16C A magnified view of the framed area. For example... Figure 16C As shown, the detected peak potentials are asynchronous and there is no crosstalk between adjacent channels. A custom peak potential sorting algorithm is used to identify individual neuron activity. The threshold for peak potential detection is set to five times the standard deviation of the filtered (300-6000Hz bandpass) time series, and dimensionality reduction is performed using principal component analysis. MATLAB's "kmeans" function is used to cluster the extracted waveforms and remove noise artifacts. Figure 16D Peak potential sorting analysis is presented, showing the waveforms (left) and raster maps (right) of multiple neurons simultaneously recorded by this brain probe. Meanwhile, Figure 16E The evolution of signals recorded by the same electrodes at 1 and 2 weeks post-implantation is shown (left side shows filtered voltage recordings, right side shows the detected average waveform). The recorded individual neuronal activity stabilized more than two weeks later, with no significant change in the signal-to-noise ratio. Figures 16A-16E The stars in all the diagrams represent voltage artifacts.

[0200] Example 9

[0201] This embodiment demonstrates the preparation of fluorinated polymer precursor solutions of poly(1,1,1,3,3,3-hexafluoroisopropyl acrylate) (PHFIPA) and poly[2-(perfluorohexyl)ethyl]acrylate (PPFHEA). MD700 is a bifunctional PFPE-urethane methacrylate, purchased from Solvay, and used as a crosslinking agent. 2-Hydroxy-2-methylphenylacetone was used as a photoinitiator. The monomers, crosslinking agent, and photoinitiator of each polymer were mixed in a weight ratio of 100 / 1 / 0.5 to prepare a precursor solution for spin-coating PHFIPA and PPFHEA. A concentration of 100 to 200 mJ / cm² was used. 2 UV exposure dose (wavelength 365nm) is used to crosslink PHFIPA and PPFHEA films.

[0202] Example 10

[0203] This example demonstrates that a fluorinated polymer (e.g., perfluoropolyether) layer exhibits a high electrochemical impedance modulus after prolonged exposure to a brine solution. This example compares the decrease in the specific electrochemical impedance modulus of the polymer after prolonged immersion in a 10x phosphate buffer solution at 65°C, and is similar to the tests described under these conditions in Example 4. Layers such as poly(1,1,1,3,3,3-hexafluoroisopropyl acrylate) (PHFIPA), poly[2-(perfluorohexyl)ethyl]acrylate (PPFHEA), and PFPE-DMA are compared with layers of polydimethylsiloxane (PDMS), styrene-ethylene-butene-styrene (H-SEBS), polyimide (PI), polyisobutylene (PIB), and SU-82000.5 epoxy photoresist (used as a comparative in this example).

[0204] Electrochemical impedance spectroscopy was performed as described above. The polymer layer was immersed in 10x phosphate-buffered saline (PBS) under rapid aging conditions at 65°C. Figure 17A The specific electrochemical impedance modulus (top) and phase (bottom) of the dielectric polymers under pristine conditions and after aging in 10xPBS at 65 °C were plotted (for PFPE-DMA, PHFIPA, PPFHEA, PDMS, H-SEBS, PI, SU-8, t / H). 2 =5 days / micrometer 2 and for PDMS t / H 2 = 1.55 days / micrometer 2 ). Figure 17B and 17C The immersion layer, measured at 1 kHz and 1 Hz, is presented as a function of time (via H). 2 The electrochemical impedance modulus (ESM) is standardized. Under rapid aging conditions, the ESM of all polymers decreases. However, the ESM of fluoropolymer layers (PFPE-DMA, PPFHEA, and PHFIPA) remains relatively stable. Figure 17B-17C The specific electrochemical impedance modulus (SEM) of the fluorinated polymers (highlighted in bold) (very similar to that of the SU-8 layer) decreases very slowly compared to that of other polymers (PIB, PI, H-SEBS, and PDMS). These data demonstrate that fluorinated polymers generally exhibit long-term stability under physiological saline conditions.

[0205] Example 11

[0206] This embodiment illustrates an exemplary method for manufacturing a brain probe comprising a fluorinated polymer (e.g., a perfluoropolyether) according to certain implementations. The exemplary method is... Figure 18The method is similar to that described in Example 5 above. Unless otherwise stated, all photoresists and developers are obtained from MicroChem Corporation.

[0207] 1. Rinse and dry a 3-inch thermally oxidized silicon wafer (from University Wafer) with acetone, IPA, and water. Then dehydrate at 110°C for 3 minutes and treat with O2 plasma at 100W, 40 sccm O2 for 1 minute. Spin-coat hexamethyldisilazane (HMDS), adhesion promoter, LOR 3A photoresist, and S1805 photoresist onto the wafer at 4000 rpm / s for 1 minute. Hard bake the LOR 3A photoresist at 180°C for 5 minutes, then apply the S1805 photoresist and hard bake at 115°C for 1 minute. Then heat the photoresist at 40 mJ / cm². 2 Expose under UV light and develop with CD-26 developer for 70 seconds, rinse with DI water and dry. Then, deposit a 100 nm Ni layer on the wafer using a thermal evaporator and strip it in Remover PG for 3 hours.

[0208] 2. SU-8 2010 epoxy resin was used to fabricate spacers. SU-8 2010 was spin-coated onto the wafer at 3000 rpm / s for 2 minutes, followed by pre-baking at 60°C for 2 minutes and then at 95°C for 4 minutes. SU-8 2010 epoxy resin was treated with 170 mJ / cm². 2 UV exposure, followed by baking at 60°C for 2 minutes and then at 95°C for 2 minutes and 30 seconds. Finally, SU-8 2010 epoxy resin was developed in SU-8 developer for 2 minutes, rinsed with IPA, dried, and hard-baked at 180°C for 1 hour.

[0209] 3. Using the same stripping method described in step 1, deposit the Cr / Au (15 / 100nm) I / O pad of the brain probe by electron beam evaporation.

[0210] 4. First, clean the wafer with IPA and water and dry it. Then, spin-coat the PFPE-DMA precursor onto the wafer at 2000-6000 rpm / s for 1 minute and pre-bake at 115°C for 2 minutes to obtain a thickness of 500 nm to 3 μm, depending on the spin speed and precursor concentration. Using the exemplary custom nitrogen diffuser described in Example 5, align the spin-coated PFPE-DMA film in a photomask aligner and apply 10-30 mJ / cm⁻¹. 2UV patterning was then performed. The PFPE-DMA pattern was then post-baked at 115°C for 1 minute and developed in a developer (bis(trifluoromethyl)benzene:1,1,1,3,3-pentafluorobutane, volume ratio 1:3) for 1 minute, followed by drying. O2 plasma was used to clean the pattern. Finally, the PFPE-DMA pattern was hard-baked at 150°C for 1 hour.

[0211] 5. Activate the PFPE-DMA surface with plasma of 20-30W power and 40sccm argon flow rate for 2-6 minutes.

[0212] 6. As described in step 1, pattern the wafer with LOR 3A photoresist and either S1805 or S1813 photoresist. Apply a subsequent plasma treatment again before metal sputtering. Deposit metal films of different combinations, such as Al / Au, Al / Au / Al, Al / Au / Pt, Cr / Au, and Cr / Au / Cr, with each layer thickness ranging from 20 to 100 nanometers. Finally, the metal layers are stripped overnight in Remover PG. To remove stripping residue, a spray gun equipped with the remover PG is used.

[0213] 7. Spin-coat PFPE-DMA and UV cure, followed by plasma surface treatment, resist stripping patterning and metal sputtering to create additional layers for interconnects, as shown in steps 4-6.

[0214] 8. Pattern the top PFPE-DMA layer using the method described in step 4.

[0215] 9.( Figure 18 (Optional steps not shown). SU-8 2010 (with a thickness selected based on the total thickness of the brain probe) is used to define a frame for retaining the soft brain probe during release. An exemplary plastic frame is referenced in Embodiment 8 above. Figure 14 It has been described.

[0216] 10.( Figure 18 (Optional steps not shown). To connect the soft brain probe to the recording device, metal electrodes are sequentially deposited from PFPE-DMA onto a silicon dioxide substrate using isotropic deposition of metal, thereby achieving standard flip-chip bonding of flexible cables.

[0217] Example 12

[0218] This embodiment demonstrates the characteristics of an exemplary brain probe manufactured using the method of Example 9. Figure 19 Bright-field (BF) optical images are presented, showing an exemplary brain probe comprising a six-layer PFPE-DMA sandwiched with four exemplary metal electrodes. Figure 19The smaller images show the electrodes in more detail. For PFPE-DMA characteristics, this exemplary brain probe has a lateral resolution of approximately 1 micrometer and a controllable thickness in the range of 0.3–3 micrometers. Focused ion beam (FIB) milled SEM of the cross-section of the exemplary brain probe shows no delamination between the PFPE-DMA and the metal layer, even after uniaxial stretching to 20% elongation.

[0219] The brain probe was then chip-bonded to connect it to the recording device. After chip bonding, PEDOT:PSS or Pt black was applied to the electrode tips using standard electroplating techniques to verify electrode conductivity. Electrodeposition was performed using a Bio-logic SP-150 potentiostat and its commercial software EC-lab for voltage or current control. The electrodes of the brain probe were connected to the working electrodes. A platinum wire immersed in the precursor solution served as the counter electrode and also as a voltage reference. For platinum black deposition, the precursor solution consisted of 1 mM chloroplatinic acid solution and 25 mM sodium nitrate. Cyclic voltammetry was used, where the potential was varied from -1.0 V to 0.2 V at 0.05 V / s for 10-15 cycles. For PEDOT-PSS deposition, an electrolyte consisting of an aqueous solution of 0.01 M PEDOT (Sigma-Aldrich, USA) and 0.1 M PSS sodium (Sigma-Aldrich, USA) was used. The electrochemical polymerization reaction was carried out under constant voltage conditions. In constant voltage mode, polymerization was carried out at a constant current of 1 V for 30 seconds.

[0220] Figure 20 The changes in impedance modulus of the 40 μm diameter electrode of the brain probe before and after PEDOT:PSS and Pt black plating at 1 kHz are presented (n = 32, bar graphs show mean ± SD). In both cases, the p-value of the paired two-tailed t-test was <0.0001, indicating that either PEDOT:PSS or Pt black coating resulted in a significant decrease in impedance, indicating normal contact function.

[0221] The impedance of the sputtered Al / Au interconnects and Pt electrodes was measured over time to confirm the stability of the exemplary brain probe. Results are as follows: Figure 21 As shown in the figure, the exemplary brain probe did not experience significant impedance changes over time. The stability of the interconnect impedance demonstrates the long-term stability of the electrodes.

[0222] The elastic modulus of the exemplary brain probe was determined, and the exemplary brain probe was compared with other prior art brain probes in terms of their elastic modulus (E). d The results were compared in terms of both the number of electrodes and their electrode number density (the number of electrodes created per square micrometer of brain probe). Figure 22A comparison of the elastic modulus and electrode number density of the brain probe is shown, with the elastic modulus of typical brain tissue indicated by shaded areas. Figure 22 As shown, the exemplary electrode described herein has the lowest elastic modulus of all brain probes. Furthermore, the exemplary brain probe described herein has a 100-fold electrode number density compared to prior art electrodes with similar elastic modulus. The elastic modulus of the exemplary brain probe described herein is approximately 1 / 1000 of the elastic modulus of prior art brain probes with similar electrode number density. The ratio between the electrode number density and elastic modulus of the exemplary brain probe described herein exceeds 10. -8 Electrodes / micrometer 2 -Pa. Conversely, the ratio between the electrode number density of prior art brain probes and the elastic modulus of exemplary brain probes is in the range of 10. -12 Electrodes / micrometer 2 -Pa and 10 -10 The number of electrodes per micrometer is between 2-Pa. This indicates that, compared to other prior art brain probes, the exemplary brain probe described herein achieves superior mechanical properties and high sensor density.

[0223] Example 13

[0224] In this embodiment, the adhesive strength between two exemplary PFPE-DMA layers bonded by the method of Example 9 is measured by using a 90° peel test performed at peel rates of 0.1 mm / s, 1 mm / s, and 10 mm / s. Figure 23 A schematic diagram of the peel test is presented, and Figure 24 The adhesion energy of the top PFPE-DMA layer to the PFPE-DMA substrate is shown, or, by comparison, to the adhesion energy to glass. The fracture toughness of PFPE-DMA is also reported. Figure 24 In the middle. For example Figure 24 As shown, the self-adhesion energy of the PFPE-DMA layer significantly exceeds its adhesion energy to the glass substrate (36.0 ± 0.5 J / m at a peel rate of 0.1 mm / s). 2 and 4.9±0.7J / m 2 It is closer to the inherent fracture toughness of the two layers (measured at 128 J / m). 2 and 261J / m 2 The result indicates that the two PFPE-DMA layers are firmly bonded and do not easily delaminate under strain.

[0225] Example 14

[0226] In this embodiment, the interconnect resistance of the exemplary brain probe was measured on a substrate and in independent configurations under strain-free and uniaxial strain conditions. Figure 25The interconnect resistance of each brain probe on the substrate is shown after release from the substrate and under 2% (λ = 1.02) and 5% (λ = 1.05) uniaxial tension. As shown, the interconnect resistance is consistent under all conditions and remains high even at 5% strain.

[0227] Example 15

[0228] In this embodiment, finite element analysis (FEA) was used to model an exemplary brain probe to understand its mechanical properties. The mechanical properties of different polymer brain probes were analyzed using Abaqus 6.12 software. The simulation aimed to evaluate the strain and stress concentration of a composite beam bending around a capillary with a circular cross-section under gravity. The brain probe was modeled using a three-layer design: a 140 nm thick central metal layer between two 4.5 μm thick dielectric layers, with an elastic modulus of PFPE-DMA or SU-8. The elements used were S4R5 or S4R, with a mesh size of 50 μm. The contact between the probe and the capillary was modeled solely by inter-surface normal forces (no shear contact).

[0229] Multilayer devices encapsulated with dielectric elastomers are more flexible than those made of plastic dielectric materials. Comparing a 9 μm thick PFPE-DMA with the SU-8 brain probe containing a 100 nm thick metal interconnect layer, the PFPE-based brain probe exhibits greater flexibility. Finite element analysis confirms the difference in flexibility due to the different elastic moduli between the elastomer and the rigid dielectric material. The contribution of the dielectric elastomer to the load-bearing capacity is negligible, thus the metal layer becomes the primary load-bearing component. As a result, a simple beam model shows that this design reduces the bending stiffness of the brain probe by four orders of magnitude.

[0230] Finite element analysis further revealed that when a single-layer, 9 μm thick PFPE-DMA brain probe was bent under gravity around a 1 mm diameter capillary, the strain concentration of the central metal layer (~0.003) remained significantly lower than the yield strain of Au. This simulation indicates that the metal interconnects do not undergo plastic deformation or fracture when the soft brain probe is bent. The adhesion between the metal wires and the elastomer was also sufficient to produce a wrinkle pattern, a common feature in laminates containing islands of rigid material on a soft substrate, where a larger strain can be accommodated before the rigid layer fails, compared to the independent fracture strain. This result further explains why the metal connectors of the exemplary brain probe described herein maintain high conductivity after 5% uniaxial strain.

[0231] Since brain probes can generally be multi-layered, multi-layered composite models are evaluated to model multi-layered models of different thicknesses. Figure 26 A composite beam model of a brain probe with 2N-1 layers of metallic interconnects is presented. It is assumed that the layers, made of the same material, have the same thickness. The variable h...d and h m These represent the thickness of the dielectric packaging layer and the metal layer, respectively. For model purposes, the layer thickness value is chosen as h. d =2 micrometers and h m =40nm. As shown, strain ε xx The values ​​vary throughout the composite beam. The actual values ​​of the metal's elastic modulus and Poisson's ratio are E... 金属 =79GPa and ν 金属 =0.22. To model composite beams containing rigid plastics (e.g., SU-8), the value E is chosen. 塑料 =4GPa and ν 塑料 =0.33 were used as actual estimates for the elastic modulus and Poisson's ratio, respectively. To model the rigid composite beam containing the elastic body, E was selected as... 弹性体 =0.5MPa and ν 弹性体 The actual value of 0.5 is used for elastic modulus and Poisson's ratio.

[0232] The flexural stiffness of the composite beam is estimated as a function of the number of layers in the composite beam. Figure 27 The results presented show that rigid plastic beams have significantly higher bending stiffness than elastic beams. As shown in the figure, with increasing metal layers, the bending stiffness of the elastic composite beam approaches that expected for a single metal layer, indicating that the bending stiffness of the thick brain probe will be limited by the bending stiffness of the metal layers, rather than the bending stiffness of the polymer layers. Figure 28 The ratio of the flexural stiffness of rigid plastic beams and elastic beams as a function of the number of metal layers is presented. As the number of metal layers increases, the ratio of the flexural stiffness of rigid plastic composite beams to elastic composite beams approaches the asymptotic limit of 0.28, which is due to the contribution of the metal layers to the flexural stiffness of both types of composite beams.

[0233] Example 16

[0234] This embodiment illustrates a method for transferring and aligning an exemplary brain probe using an exemplary framework of the type described in previous embodiments. Figure 29A A perspective schematic diagram of an exemplary brain probe 502 in an exemplary framework 504 according to some embodiments is presented. A shuttle 506 (in this case, a tungsten shuttle) is also shown for applying the exemplary brain probe. Figure 29BA side view schematic diagram of an exemplary method for inserting a brain probe is presented. In step I, a shuttle 506 is used to insert a brain probe 502 into brain tissue while a frame 504 holds the brain probe 502 in place. In step II, the shuttle is removed. In step III, the frame 504 is removed from the brain probe 502, which remains in the brain tissue. Finally, in step IV, dental adhesive 508 is applied to seal the brain probe 502 in place while allowing communication between the brain probe and the recording device. This method allows the exemplary brain probe of Example 12 to be implanted into the brain of a mouse. The soft probe is implanted in the somatosensory cortex region and connected to a voltage amplifier via a flat, flexible cable for electrophysiological recording, as described in more detail below.

[0235] Example 17

[0236] This embodiment demonstrates the implantation of an exemplary brain probe into the mouse brain and the subsequent measurement of brain activity. The brain probe is inserted according to the methods described in Examples 8 and 16. Figure 30 Representative spontaneous activity from the 16-channel PFPE-DMA is shown one month post-implantation. Data were analyzed at two-week intervals using peak potential sorting analysis. Figure 31 The results of peak potential sorting analysis are shown, illustrating the average waveform of action potentials in representative units. The recorded activity of individual units remained stable over 10 weeks post-implantation, with minimal change in waveform shape and peak potential intervals throughout the period. Principal component analysis (PCA) further demonstrates the stability of the brain probe, showing that all units exhibited nearly constant positions in the first and second principal component planes (PC1-PC2) from 2 to 10 weeks post-implantation. This is... Figure 32 As shown in the image, it displays the relationship with... Figure 32 The cell positions of several channels in the PC1-PC2 plane are associated with the channel and time.

[0237] Figure 33A The average noise level for all channels is presented, which is low and nearly constant after implantation. (For n = 16 electrodes, the noise level was 10.4 ± 1.8 μV at 2 weeks post-implantation and 11.8 ± 1.8 μV at 10 weeks post-implantation.) Figure 33A (as shown in the image). Figure 33B The average peak potential amplitude across all channels is presented, showing a slight increase 10 weeks post-implantation, primarily due to activity within individual channels. (For n = 8 units, the peak amplitude was 119.7 ± 19.2 μV at 2 weeks post-implantation and 160.6 ± 55.3 μV at 10 weeks post-implantation). These results indicate that the brain probe functioned as expected, without substantial degradation within 10 weeks.

[0238] Finally, to test the immunoreactivity of the size-modified brain probes, the immunoreactivity in mice was investigated in response to exemplary implanted 9-micrometer-thick PFPE-DMA and SU-8 brain probes, which could integrate at least 4–8 layers of electrodes in the mouse brain. Immunohistochemical analysis of brain sections was performed at 2, 6, and 12 weeks post-implantation to assess the immunoreactivity to the implanted brain probes. SU-8 probes of the same size were implanted as controls (n = 4 mice at each time point).

[0239] Immunohistochemistry and confocal fluorescence imaging were performed. Mice were anesthetized with 40–50 mg / kg sodium pentobarbital at each time point (2, 6, and 12 weeks post-implantation), then perfused with 40 mL of 1xPBS and 40 mL of 4% paraformaldehyde, followed by decapitation. Brains implanted with the exemplary brain probe were removed from the skull and post-fixed in paraformaldehyde at 4°C for 24 hours. The brains were transferred to a sucrose solution (concentration gradually increased from 10% to 30%, w / v) until they sank to the bottom. Samples were embedded in a compound at the optimal cutting temperature (OCT) and sliced ​​into 30 μm thick sections using a cryostat. Brains implanted with the same thickness of the SU-8 brain probe were used as a comparison.

[0240] First, brain sections were incubated with primary antibodies: NeuN (for neuronal nuclei, 1:200, Abcam#ab177487, USA), GFAP (for astrocytes, 1:200, Abcam#ab4674, USA), and IBA1 (for microglia, 1:100, Abcam#ab5076, USA) overnight at 4°C. After washing three times with 1xPBS, the brain sections were incubated with secondary antibodies at room temperature for 3–4 hours. The brain sections were then stained with 4',6-diamidinylphenylindole 8 (DAPI) for 10 minutes. Finally, after washing with 1xPBS, all samples were imaged using a Leica TCS SP8 confocal microscope.

[0241] Images at 2, 6, and 12 weeks post-implantation showed significantly enhanced NeuN (neuronal) signaling around the PFPE-DMA probe compared to the SU-8 probe (p<0.05, n=4, two-tailed unpaired t-test). Specifically, NeuN intensity increased to intrinsic levels at 12 weeks post-implantation (92.7±14.0% vs. 61.6±16.9%, mean ± SD, n=4), indicating high biocompatibility of the PFPE-DMA probe. Fluorescence intensity in astrocytes and microglia at 12 weeks post-implantation showed a significant reduction around the exemplary PFPE-DMA brain probe compared to the SU-8 probe (GFAP: 111.7±27.7% vs. 303.7±62.6%, Iba-1: 15.5±24.6% vs. 156.4±21.7%, mean ± SD, n=4). These results demonstrate the high biocompatibility of PFPE-DMA dielectric elastomers and their ability to further increase electrode density in chronic brain implantation.

[0242] Figure 34 We report the normalized mean fluorescence intensity as a function of distance from the probe boundary for neurons (NeuN), astrocytes (GFAP), and microglia (IBA-1) at 2, 6, and 12 weeks post-implantation. Fluorescence intensity at distances from the probe surface from 525–550 μm was used to normalize the data. Reported values ​​are mean ± SD, n = 4, *p < 0.05; **p < 0.01; ***p < 0.001, two-tailed unpaired t-test.

[0243] These results demonstrate the long-term biocompatibility and functionality of the exemplary PFPE-DMA brain probe described in this paper.

[0244] While several embodiments of the invention have been described and illustrated herein, those skilled in the art will readily conceive of various other methods and / or structures for performing the stated functions and / or obtaining the results and / or one or more advantageous aspects described herein, and each such variation and / or modification is considered to be within the scope of the invention as described herein. More generally, those skilled in the art will readily understand that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary and that actual parameters, dimensions, materials, and / or configurations will depend on the specific application of the teachings of the invention. Those skilled in the art will recognize or be able to identify many equivalents of the particular embodiments of the invention described herein (through no more than conventional experimentation). Therefore, it should be understood that the foregoing embodiments are presented by way of example only, and that the invention may be practiced in ways different from those explicitly described and claimed within the scope of the appended claims and their equivalents. The invention relates to various individual characteristics, systems, articles, materials, and / or methods described herein. Furthermore, any combination of two or more such characteristics, systems, articles, materials, and / or methods is included within the scope of the invention if such characteristics, systems, articles, materials, and / or methods are not contradictory.

[0245] Unless explicitly indicated otherwise, the indefinite articles “a” and “an”, as used herein in the specification and claims, shall be understood to mean “at least one”.

[0246] The phrase “and / or,” as used herein in the specification and claims, should be understood to mean “any one or both” of the connected elements, that is, elements present together in some cases and separately in others. In addition to the elements explicitly identified by the “and / or” clause, other elements may optionally be present, whether related to or unrelated to those explicitly identified, unless expressly indicated otherwise. Thus, as a non-limiting example, a reference to “A and / or B,” when used in conjunction with open-ended terms such as “comprising / including,” may refer to A without B (optionally including elements other than B) in one embodiment; to B without A (optionally including elements other than A) in another embodiment; to A and B (optionally including other elements) in yet another embodiment; and so on.

[0247] As used herein in the specification and claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when items are separated in a list, “or” or “and / or” should be understood to be inclusive, i.e., including at least one, but also including more than one of a plurality of elements or a list of elements, and optionally, including additional items not listed. Only when the opposite terms are explicitly specified, such as “only one of…” or “exact one of…” or, when used in a claim, “consisting of…”, will refer to including a plurality of elements or exactly one of a list of elements. Generally, the term “or” as used herein should be interpreted as indicating an exclusive choice (i.e., “one or the other but not both”) only when preceded by exclusive terms such as “any,” “one of…,” “only one of…,” or “exact one of…”. “Substantially consisting of…”, when used in a claim, should have its ordinary meaning as used in the field of patent law.

[0248] As used herein in the specification and claims, the phrase “at least one” relating to a list of one or more elements should be understood to mean at least one element selected from any one or more elements in the list, but does not necessarily include at least one of every element expressly listed in the list of elements and does not exclude any combination of elements in the list of elements. This definition also allows for the optional presence of elements other than those expressly identified in the list of elements referred to by the phrase “at least one,” whether related to or unrelated to those expressly identified elements. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B” or, equivalently, “at least one of A and / or B”) may in one embodiment mean at least one (optionally including more than one) A without the presence of B (and optionally including elements other than B); in another embodiment, mean at least one (optionally including more than one) B without the presence of A (and optionally including elements other than A); in yet another embodiment, mean at least one (optionally including more than one) A and at least one (optionally including more than one) B (and optionally including other elements); and so on.

[0249] Some implementations can be embodied as a method, and various examples of such methods have been described. Actions performed as part of the method can be ordered in any suitable manner. Thus, an implementation can be constructed in which actions are performed in a different order than those shown, which may include (e.g., more or fewer) actions different from those described, and / or may involve performing some actions simultaneously, even though in the implementations specifically described above, the actions are shown as being performed sequentially.

[0250] The use of ordinal terms such as “first,” “second,” and “third” to modify a claim element does not imply any priority, sequence, or order of one claim element relative to another, or the chronological order of the actions of the method. Rather, it serves only as a label to distinguish one claim element with a specific name from another element with the same name (but using ordinal terms), thus differentiating the claim elements.

[0251] In the claims, and in the foregoing description, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “owning,” “involved in,” “holding,” etc., are understood to be open-ended, meaning including but not limited to. Only the transitional phrases “consisting of” and “consisting substantially of” shall be closed or semi-closed transitional phrases, respectively, as illustrated in Section 2111.03 of the U.S. Patent Examination Procedure Manual.

Claims

1. An article configured for implantation in a subject's organ or brain tissue, comprising: A first layer comprising a first fluorinated polymer; A second layer comprising a metal or metal alloy bonded to the first layer; and A third layer, which is bonded to the second layer, contains a second fluorinated polymer. in: The first fluorinated polymer and / or the second fluorinated polymer have a weight-average molecular weight greater than 20 kg / mol, and The first fluorinated polymer and / or the second fluorinated polymer exhibit a decrease in specific electrochemical impedance modulus of no more than 50% at 1 kHz after immersion in 1x phosphate buffer at 37°C for at least 100 days and / or immersion in 10x phosphate buffer at 70°C for 5 days.

2. The article of claim 1, wherein the first fluorinated polymer is the same as the second fluorinated polymer.

3. The article of claim 1, wherein the first fluorinated polymer is different from the second fluorinated polymer.

4. The article of claim 1, wherein the organ is the brain.

5. The article of claim 1, wherein the second layer comprises aluminum.

6. The article of claim 1, wherein the second layer comprises gold.

7. The article of claim 1, wherein the first fluorinated polymer and / or the second fluorinated polymer are crosslinked.

8. The article of claim 1, further comprising one or more additional layers.

9. The article of claim 1, wherein the first layer has a thickness of at least 0.3 micrometers and less than or equal to 3.0 micrometers.

10. The article of claim 1, wherein the first fluorinated polymer and / or the second fluorinated polymer is patterned.

11. The article of claim 10, wherein the pattern of the first fluorinated polymer and / or the second fluorinated polymer has a lateral resolution of 5 micrometers or less.

12. The article of claim 1, wherein the first fluorinated polymer and / or the second fluorinated polymer exhibits elastic tensile deformation equal to or greater than 20% strain.

13. The article of claim 1, wherein the article of claim 1 is part of the apparatus.

14. The article of claim 1, wherein the article of claim 1 is a sensor.

15. The article of claim 14, wherein the article is a neural activity sensor.

16. The article of claim 1, wherein the first fluorinated polymer and / or the second fluorinated polymer exhibit a decrease in specific electrochemical impedance modulus of no more than 50% at 1 kHz after immersion in a 1x phosphate buffer solution at 37°C for 450 days.

17. The article of claim 1, wherein the article comprises a plurality of electrodes.

18. The article of claim 1, wherein the first fluorinated polymer and / or the second fluorinated polymer has a content of less than or equal to 10. 6 The elastic modulus of Pa.

19. The article of claim 1, wherein the first fluorinated polymer and / or the second fluorinated polymer are independently selected from perfluoropolyether (PFPE), perfluoropolyether dimethacrylate (PFPE-DMA), polytetrafluoroethylene (PTFE), fluorinated ethylene-propylene (FEP), perfluoroalkoxy polymer (PFA), polychlorotrifluoroethylene (PCTFE), tetrafluoroethylene propylene (TFE), poly(1,1,1,3,3,3-hexafluoroisopropyl acrylate) (PHFIPA), and poly[2-(perfluorohexyl)ethyl]acrylate (PPFHEA).

20. Use of the article of any one of claims 1-19, comprising: The article is inserted into the subject's organ or brain tissue.

21. The use of claim 20, wherein the organ is the brain.

22. A method for manufacturing an article of any one of claims 1-19, comprising: Fluorinated polymers are deposited on a substrate; An inert gas plasma is applied to the fluorinated polymer to form the treated fluorinated polymer; and The material is deposited onto the treated fluoropolymer.

23. The method of claim 22, wherein the inert gas plasma comprises argon or nitrogen.

24. A method for manufacturing an article of any one of claims 1-19, comprising: Fluorinated polymers are deposited on a substrate; Treat fluoropolymers to make them easier to deposit; and The second fluorinated polymer is deposited onto the treated fluorinated polymer.

25. A method for manufacturing an article of any one of claims 1-19, comprising: Fluorinated polymers are deposited on a substrate; Treat fluoropolymers to make them easier to deposit; and The material forming multiple electrodes is deposited onto the treated fluorinated polymer.

26. Use of the article of claim 17, comprising: The plurality of electrodes are used to determine electrical signals, wherein the plurality of electrodes are at least partially contained within the subject.

27. Use of the article of claim 17, comprising: The plurality of electrodes are used to determine the electrical activity of individual cells within the subject, wherein at least a portion of the plurality of electrodes is in contact with the cells for at least 5 days.

28. The use of claim 27, wherein the cell is a neuron.

29. Use of the article of claim 17, comprising: The cells within the subject are electrically stimulated using the plurality of electrodes.

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