Minimally invasive electrocorticogram brain-computer interface

Abstract

A guidewire driven brain-computer interface system for minimally invasive implantation is provided that includes a flexible electrode array and a plurality of flexible guidewires attached to the flexible electrode array. The flexible electrode array comprises a plurality of insulated poly-p-xylylene-C layers, metal interconnection lines and electrodes. The plurality of flexible guidewires are configured to be guided by an external mechanical force such that the flexible electrode array passes through a craniotomy field and is deployed by tracking the plurality of flexible guidewires. The flexible guidewires each include a manipulation tip and a pull wire.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 564,204, filed on March 12, 2024, the entire contents of which, including any drawings, tables, or diagrams, are hereby incorporated by reference herein. Technical Field

[0003] The present invention relates to a guidewire-driven brain-computer interface (GD-BCI) system and method for minimally invasive implantation. Background Art

[0004] Bidirectional brain-computer interface (BCI) has made significant contributions to basic neuroscience research and clinical applications, covering areas such as vision 1-4 , sensory motor 5,6 and auditory nerve prosthesis 7,8 fields, and epilepsy 9,10 and Parkinson's disease 11 Among them, the electrocorticographic brain-computer interface (ECoG-BCI) uses surface electrode implants to collect neural signals from the brain surface 12,13 Compared with scalp EEG and intraparenchymal single-neuron recording, ECoG-BCI achieves an optimal compromise between signal acquisition and surgical invasiveness, thus becoming the gold standard for neuroscience clinical data collection and human individual research. 14-16 .

[0005] Enhancing the recording range and density of ECoG-BCI is crucial for analyzing correlated activity between multiple brain regions. 17 , improve signal decoding accuracy 18,19 and accurately identify neurological disease foci 20 Traditionally, implanting ECoG-BCIs covering a large area requires an equally large skull opening. 21,22 , which exposes a large amount of brain tissue to the outside environment. This can cause brain tissue to swell. 23 , inflammation 24 , increasing cortical damage 25 and infection 26 risk of delaying the acceptance of potential BCI users and patients 27,28 .

[0006] To mitigate these risks and extend the benefits of ECoG-BCI to a wider patient and user population, various minimally invasive surgical techniques have been developed. These techniques include pressure-driven actuation 29 , magnetic assisted positioning 30 , skull micro-suture insertion 31 and shape memory alloy actuation 32 These reported methods can deploy devices larger than the open skull hole. 29,30,32 Or implant a high-density device through the skull suture 31 However, a method that achieves broad coverage and high density with minimal invasiveness has not yet been reported. Summary of the Invention

[0007] There is still a need in this field to improve the design and technology of minimally invasive electrocorticographic brain-computer interfaces.

[0008] According to an embodiment of the present invention, a guidewires-driven brain-computer interface (GD-BCI) system for minimally invasive implantation is provided. The system includes a flexible electrode array and a plurality of flexible guidewires attached to the flexible electrode array. The flexible electrode array includes a plurality of insulating parylene-C layers, metal interconnects, and electrodes made of PEDOT:PSS / pHEMA and gold. Adjacent metal interconnects are spaced apart by a distance of 10 μm. The metal interconnects are formed of gold and are completely encapsulated between adjacent insulating parylene-C layers. In addition, the density of the flexible electrode array is 28.4 electrodes / cm 2 . In addition, the flexible electrode array is formed of a biocompatible material, and the biocompatible material includes one or any one of parylene-C, poly(2-hydroxyethyl methacrylate) (pHEMA), polydimethylsiloxane (PDMS) and polyvinyl acid (PGA). The flexible electrode array includes 256 microelectrodes. Each of the multiple insulating parylene-C layers includes multiple perfusion holes. In addition, multiple flexible guide wires are attached to the corner segments of the parylene-C layer of the flexible electrode array. The multiple flexible guide wires are configured to be guided by an external mechanical force so that the flexible electrode array passes through the craniotomy area and is deployed by tracking the multiple flexible guide wires. The multiple flexible guide wires each include a manipulation tip and a traction wire. The traction wire is an absorbable surgical suture made of polyvinyl acid (PGA) and can be absorbed by the human body.

[0009] In certain embodiments of the present invention, a method for deploying a guidewire-driven brain-computer interface (GD-BCI) system for minimally invasive implantation is provided. The method includes guiding multiple flexible guidewires of the GD-BCI system and positioning a flexible electrode array of the GD-BCI system in the subdural space or the epidural space, wherein the multiple flexible guidewires are attached to the flexible electrode array. Each of the multiple flexible guidewires is individually controlled by an external mechanical force through a first opening and exits through a second opening. In addition, when the traction wire of the guidewire is drawn out from the second opening, the flexible electrode array is positioned by pulling the traction wire. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1A A conceptual perspective view shows a device implanted in the subdural space through four millimeter-scale skull windows to stimulate the cortex and collect ECoG signals. Figure 1B The fabricated GD-BCI system is shown connected to a skull base compatible with a Blackrock cereport headstage, wherein the GD-BCI system includes three traction wires capable of navigating between the dura and pia mater, and Figure 1C An exploded illustration of a thin film electrode array architecture according to an embodiment of the present invention is shown, showing the insulating parylene-C (DPX-C) layer, gold interconnects, and PEDOT:PSS / pHEMA electrodes, where the sensing area is 30 mm × 30 mm and has 256 channels.

[0011] Figure 2A is a schematic diagram of the manipulator tip guided within the subdural space. Figure 2B is a schematic diagram of a folded GD-BCI system that is implanted through a millimeter-scale skull window and deployed in the brain by retracting three traction wires, and Figure 2C Photographic images showing a GD-BCI system deployed in a phantom brain model according to an embodiment of the present invention.

[0012] Figures 3A-3G The procedure for implanting a GD-BCI into the right cortex of a beagledog is shown. Figure 3A is an optical image of a pre-processed beagle head with four skull openings. Figures 3B-3C The manipulation process of the steering tip and the pull wire is shown. Figures 3D-3E The process of deploying a thin-film electrode array by tracking three pull wires is shown. Figures 3F-3G An implanted GD-BCI is shown according to an embodiment of the present invention.

[0013] Figure 4A schematic diagram of a real-time recording and decoding system of a GD-BCI device implanted in an individual's brain is shown. According to an embodiment of the present invention, signals are measured in different cortical areas including the frontal lobe, motor lobe, parietal lobe, and temporal lobe.

[0014] Figures 5A-5B is a photographic image of a phantom brain model and an implanted GD-BCI system according to an embodiment of the present invention, wherein Figure 5A is a photographic image of a phantom brain model with an implanted GD-BCI system, with a scale of 25 mm, and Figure 5B Shown is a top-view image of the implanted GD-BCI system, scale bar is 20 mm.

[0015] Figure 6 The load-deformation curve of the agarose gel according to an embodiment of the present invention is shown, wherein the blue dot curve is the load-deformation curve of the agarose gel showing the mechanical properties of the micromechanical testing system, wherein the red curve is the fitting curve of the linear range of the blue curve, and wherein the fitted Young's modulus is 4964 Pa.

[0016] Figures 7A-7H The effect of the perfusion openings in establishing intimate contact with the brain phantom is shown. Figures 7A-7B are photographic images of the film device with and without the perfusion opening. Figure 7C This is an optical image of an agarose gel-based artificial brain phantom. Figures 7D-7E It shows that the GD-BCI with and without perfusion holes were placed on top of the brain phantom and tapped gently with a medical cotton ball in the same way, where the red dotted circle is the position where the GD-BCI cannot form close contact with the gyrus. Figure 7F is an optical image of red artificial cerebrospinal fluid on top of a brain phantom model. Figures 7G-7H It shows that the GD-BCI without and with perfusion holes were placed on top of the brain phantom and gently tapped with a medical cotton ball in the same way, where the yellow dotted circle is the location where CSF is trapped under the GD-BCI.

[0017] Figures 8A-8G Epidural recordings in a canine model according to an embodiment of the present invention are shown, wherein Figure 8A Figure 2 shows the location of the deployed GD-BCI device on the cortex of a beagle dog, with the dark area being the temporal lobe and the light area being the occipital lobe; Figures 8B-8C Shown are signals recorded from a beagle dog during sleep and wakefulness; Figure 8D shows the average power spectra during sleep and wakefulness; where Figure 8E Spectrograms of signals recorded by representative channels during sleep and wakefulness are shown; Figure 8FThe spatial power spectral density (PSD) patterns of the α and γ1 bands during sleep and wakefulness, as well as the PSD differences between the two states, are shown; Figure 8G Inter-channel coherence maps for different bands during sleep and wakefulness are shown. DETAILED DESCRIPTION

[0018] Embodiments of the present invention relate to guidewire-driven brain-computer interface (GD-BCI) systems and methods for minimally invasive implantation.

[0019] The terms used herein are for the purpose of describing specific embodiments only and are not intended to limit the present invention. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. As used herein, unless the context clearly indicates otherwise, the singular forms "a", "an", and "the" are intended to include plural forms as well as singular forms. It will be further understood that the term "comprising" when used in this specification specifies the presence of stated features, steps, operations, elements and / or components, but does not exclude the presence or addition of one or more other features, steps, operations, elements, components and / or groups thereof.

[0020] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning consistent with their meaning in the context of the relevant art and the present disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly defined herein.

[0021] When the term "about" is used in conjunction with a numerical value herein, it should be understood that the value may be within the range of 90% to 110% of the value, i.e., the value may be + / - 10% of the stated value. For example, "about 1 kg" means from 0.90 kg to 1.1 kg.

[0022] When describing the present invention, it should be understood that many techniques and steps are disclosed. Each of these techniques and steps has its own benefits, and each technique and step can also be used in combination with one or more of other disclosed techniques, or in some cases all of them. Therefore, for the sake of clarity, this description will avoid unnecessary repetition of each possible combination of the various steps. However, the specification and claims should be read with the understanding that such combinations are fully within the scope of the present invention and the claims.

[0023] Due to their high fidelity and non-penetrating nature, the utility of electrocorticographic brain-computer interfaces (ECoG-BCIs) has been firmly established in both clinical settings and basic neuroscience. However, existing BCI devices require compromises in terms of footprint, electrode density, surgical invasiveness, and potential risk of complications, which cannot fully meet the growing demands of advanced BCI applications.

[0024] According to an embodiment of the present invention, a deployable dual-guidewire-driven brain-computer interface (GD-BCI) system operated via a mechanically controlled guidewire is provided. The GD-BCI system can be implanted in the subdural or epidural space through a few millimeter-scale craniotomies, thereby providing a large coverage area (e.g., 9 cm 2 ) and high electrode density (e.g., 28.4 electrodes / cm 2 ).

[0025] The GD-BCI system has demonstrated its ability to chronically record and stimulate cortical activity within the canine motor cortex. Proven benefits include minimizing the risk of brain damage and complications, enhancing ECoG signal quality, and improving two-way communication. These advances are expected to expand the range of patients and users who can benefit from BCI technology.

[0026] The GD-BCI system can be implanted in the subdural space or epidural space via a few millimeter-scale craniotomy. According to an embodiment of the present invention, the GD-BCI system includes a device covering a large surface area (e.g., 9 cm 2 ) of high-density flexible PEDOT:PSS / pHEMA electrode arrays (e.g., a density of 28.4 electrodes cm -2 ), and multiple flexible guidewires, for example three. The guidewires fixed to the corners of the flexible electrode array can be introduced into the subdural space or epidural space and guided by external mechanical force. The folded flexible electrode array can be passed through the craniotomy area and unfolded by tracking the guidewires.

[0027] The thin perforated electrode array ensures excellent conformability and close contact with the contoured surface of the brain. Furthermore, deployment of the GD-BCI system within the motor cortex of a canine model demonstrated its capabilities for chronic neural signal recording, cortical electrical stimulation, and acute neural decoding. Therefore, the GD-BCI system was designed to advance the safe clinical application of BCI technology, providing the necessary coverage and electrode density for high-performance BCIs while maintaining compatibility with established clinical neurosurgical practices.

[0028] Therefore, the GD-BCI system is conducive to minimally invasive implantation of electrode arrays using guidewires, thereby achieving high-density electrode configuration (28.4 electrodes / cm 2 ) and provide wide coverage (9 cm 2Together, these features represent a significant advancement in the state of the art, presenting a unique combination of safety, precision, and effectiveness in brain-computer interfaces that was previously unattainable.

[0029] Design of the GD-BCI system

[0030] refer to Figure 1A , the GD-BCI system is engineered to achieve wide cortical coverage and a high density of recording / stimulation sites, and is designed for minimally invasive implantation on the pia mater through four millimeter-scale skull openings, significantly reducing implant-related damage. The patient-contact components of the GD-BCI system are constructed from fully biocompatible materials including poly(p-xylene-C), poly(2-hydroxyethyl methacrylate) (pHEMA), polydimethylsiloxane (PDMS), and polyvinyl acid (PGA). In addition, the GD-BCI system consists of two main components: Figure 1C The thin film electrode array shown and Figure 1C and Figure 2A Guidewire shown.

[0031] In one embodiment, the thin film electrode array is designed to smoothly navigate the subdural space, conformally adhering to the curved surface of the brain. Figure 1C As shown, the array may contain, for example, 256 microelectrodes embedded in a 10 μm thick flexible parylene C sheet, covering 9 cm with a 2 mm pitch. 2 The spatial resolution of the electrodes alleviates the problem of insufficient spatial sampling of human subdural ECoG signals and effectively decodes human speech signals. 33 .

[0032] In one embodiment, PEDOT:PSS / pHEMA was deposited onto gold microelectrodes with a diameter of approximately 0.7 mm using an electropolymerization method. The PEDOT:PSS / pHEMA electrodes can improve charge injection capacitance (CIC) and reduce interfacial impedance while maintaining good biocompatibility and biostability. They are also fine enough to deliver current stimulation and record neural activity on the cortical surface.

[0033] In one embodiment, a gold trace with a thickness of 200 nm, a width of 10 μm, a spacing of 10 μm, and a length of 3 cm was laid between the PEDOT:PSS / pHEMA electrode and the electrical connection pad, and the gold trace was completely encapsulated in two parylene C layers (5 μm bottom and 5 μm top; as shown in FIG. Figure 1CThe electrical connections utilize a land grid array (LGA) layout, which precisely bonds to the connection pads of the CerePort circular PCB on the base, minimizing the overall size of the head mount and reducing surgical trauma.

[0034] like Figure 1B As shown, the parylene-C layer of the thin film electrode array has extension sections at three corner locations for attaching guide wires that can be navigated inside the subdural space and deployed under the dura mater.

[0035] like Figures 1A-1C and Figures 7A-7H As shown, perfusion holes are patterned throughout the film in the Parylene C layer. Although the device is as thin as 10 μm, some areas of the device cannot be Figure 7D The curved brain surface structure shown in Figure 1 is consistent with that in Figure 1, and some cerebrospinal fluid (CSF) is usually retained between the tissue and the electrodes, as shown in Figure 1. Figure 7G These challenges lead to reduced signal recording consistency due to the presence of “dead zones” characterized by CSF retention, potential air bubbles, and device wrinkling. Perfusion openings can enhance the stretchability of the device, allowing the thin-film electrode array to achieve a conformal fit and maintain a tight interface with the convolutions of the sulci and gyri, as shown in Figure 2. Figure 7E In addition, the openings can also help to perfuse cerebrospinal fluid (CSF) to locations away from the electrode contacts. Therefore, a close interface is maintained between the GD-BCI and the brain surface to avoid Figure 7H Volume conduction of CSF is shown.

[0036] Deployment Demonstration in a Brain Phantom

[0037] The deployment of the GD-BCI system involves two key steps: guiding the guidewires and positioning the thin-film electrode array in the subdural or epidural space. Using surgical biocompatible guidewires, each of the three guidewires is guided through the skull opening and exits through another skull opening. Figure 2B and Figure 2C Once all three traction wires are navigated through the same skull hole and out through three different openings, the thin film electrode array can be deployed by manually pulling on the wires. The flexibility of the array enables it to be folded before insertion into the subdural or epidural space. Mechanical force is applied to the corners of the thin film electrode array via the wires. This action pulls most of the sensing area into the phantom gap, and then all three wires are pulled together to fully deploy the device on the cortical surface. The thin film electrode array with perfusion holes can be conformally attached and maintain a tight interface with the curved surface of the brain.

[0038] In vivo epidural recordings in a canine model

[0039] Figures 8B-8C Figure 3 shows high-quality micro-ECoG signals recorded by the GD-BCI during sleep and wakefulness. The average spectrum across 256 channels shows higher power levels in the alpha / beta band (e.g., 10-30 Hz) and gamma 1 band (e.g., 30-50 Hz) during wakefulness compared to sleep. Figure 8D Furthermore, power density spectra of individual channels confirmed the increase in power of α / β and γ1 oscillations during wakefulness, as shown in Figure 8E In addition, GD-BCI provides spatially resolved patterns of neural state changes, which are illustrated by power spectral density (PSD) maps in the α and γ1 bands across individual channels, as shown in Figure 8F shown.

[0040] With high spatiotemporal resolution and bandwidth, epidural recordings from GD-BCI facilitate the study of coupling between distributed brain regions under different states. Coupling between recording sites is assessed using coherence, a frequency-domain measure of linear correlation. Figure 8G The inter-channel coherence plots shown show that the gamma band, including gamma 1 (e.g., 30-50 Hz) and gamma 2 (e.g., 50-100 Hz), exhibits the lowest coherence, while the delta band shows the highest coherence in both sleep and wakefulness. This difference may be due to the fact that low-frequency signals can couple over longer distances, while high-frequency signals are more spatially confined. Notably, inter-channel coherence is higher in wakefulness than in sleep, especially from theta band to the gamma 2 band. One possible explanation for this phenomenon is that the level of consciousness is reduced during sleep, resulting in a weakened functional interaction between various cortical and subcortical areas and leading to changes and disruptions in cortical integration during information processing.

[0041] Materials and methods

[0042] Deployment Demonstration in a Brain Phantom

[0043] The deployment of the GD-BCI system involves two key steps: guiding the guidewire and positioning the thin-film electrode array in the subdural or epidural space. Figure 2A As shown, within a custom-designed 3D-printed brain phantom, each of three guide wires is guided through one skull opening and exits through another.

[0044] refer to Figure 2B and 2COnce all three pull wires have been navigated through the same skull hole and out through three different openings, the thin-film electrode array can be deployed by manually pulling on the wires. The array's flexibility enables it to be folded before insertion into the subdural or epidural space. Mechanical force is applied to the corners of the thin-film electrode array via the wires. This action pulls most of the sensing area into the phantom gap, and then all three wires are pulled together to fully deploy the device on the cortical surface. Figures 5A to 5B A GD-BCI system implanted in a brain phantom is depicted in Figure 2. Thin-film electrode arrays with perfusion holes can conformally attach and maintain a close interface with the curved surface of the brain.

[0045] Thin film electrode array manufacturing process

[0046] Thin film electrode arrays were fabricated on 4-inch Si wafers (Namkang Hi-Tech) using standard photolithography. The substrates were cleaned by reactive ion etching (RIE) using a PlasmaPro 80 under vacuum using O2 / SF6 plasma (cleaned for 10 minutes with 30 sccm O2 and 10 sccm SF6 at 200 W and 20 mT pressure), followed by O2 RIE cleaning (cleaned for 10 minutes with 30 sccm O2 at 200 W and 20 mT pressure). The cleaned substrates were then immersed in 0.5% octadecyltrichlorosilane (Sigma-Aldrich) in m-xylene (Sigma-Aldrich) for 8 hours and subsequently washed with chloroform (Sigma-Aldrich) to form a sacrificial OTS layer for lateral mechanical peeling from the substrate. A 5 μm thick poly(p-xylene)-C (DPX-C, SCS Company) was deposited by an SCS Labcoater2 for the bottom insulating layer. AZ NLOF 2020 photoresist (Microchem) was spin-coated onto the DPX-C layer at 3000 rpm for 30 seconds. After this, a pre-bake step was performed on a hot plate at 110°C for 60 seconds (Apogee baking plate). After the substrates returned to ambient temperature, they were exposed to UV light (i-line, 66 mJ cm-3) using a mask aligner (KarlSuss MA / BA6, vacuum contact). -2 ), followed by a post-bake step at 110°C for 60 seconds. The substrate was allowed to cool for a few minutes and developed in NMD238 (Microchem) for 30 seconds; it was then rinsed with DI water and air dried with compressed nitrogen. The substrate was evaporator-free using a Lesker thermal evaporator (at <6 × 10 -6Cr (20 nm thickness) and gold (200 nm thickness) were deposited on the patterned AZ NLOF 2020 photoresist under vacuum (1000 ft). Lift-off was performed using dimethyl sulfoxide (DMSO, Sigma-Aldrich). A second photolithography was performed using AZ NLOF 2070 (Microchem) to expose the Figure 1C The bottom layer of the device with the shape and infusion holes shown was spin-coated at 1500 rpm for 60 seconds and baked at 110°C for 90 seconds. They were then subjected to 196 mJ cm -2 The substrate was then etched using RIE (Oxford Plasma Pro 100RIE, 200W / O2 30 sccm) until the DPX-C exposure was complete. The device was then treated with a 0.5% silane solution (A174, SCS Company) and coated with 5 μm thick DPX-C. A third photolithography was performed using AZ NLOF 2070 to expose the DPX-C. Figure 1C The top layer of the device is shown with microelectrodes, electrical connection pads, and perfusion holes. The substrate is then etched using RIE until the metal and perfusion holes are fully exposed.

[0047] Packaging of the GD-BCI system

[0048] The electrical connections of the thin-film electrode array are patterned in a land grid array (LGA) layout that precisely matches the connection pads of the CerePort circular PCB (Blackrock) on the base. The electrical connection pads are bonded to the CerePort circular PCB using an anisotropic conductive film (DP3342MS, Dexerials) through a hot press process (150°C, 2 MPa, 6 seconds). The base is compatible with the Blackrock CerePlex preamplifier.

[0049] To deploy the GD-BCI system, three absorbable surgical sutures with a length of 10 cm were attached to the corners of the film electrodes as traction lines, as shown in Figure 1B and Figures 2A-2C As shown (R016-0, Jinhuan Medical Products Co., Ltd). 5 μL of medical grade UV curing adhesive (Loctite AA 3311) was used to attach the wire. The other side of the wire was attached with a 50 mm long flexible manipulation tip under the same conditions.

[0050] Electropolymerization of PEDOT:PSS and pHEMA

[0051] The electropolymerization method using an electrochemical workstation (Gamry Reference 600+) has been previously reported.34 PEDOT:PSS was deposited on a metal microelectrode based on a classic three-electrode cell using an aqueous solution of 3,4-ethylenedioxythiophene (EDOT, Sigma-Aldrich, 0.01 M) and polystyrenesulfonic acid (PSS, Sigma-Aldrich, 2 wt%) at a current density of 4.7 mA cm -2 , with a deposition time of 30 seconds, where the working electrode is connected to the microelectrode on the device, while the reference electrode is connected to the Ag / AgCl electrode and the counter electrode is connected to a platinum pad (10×10 mm). pHEMA deposition is then performed. It is based on a similar three-electrode electrochemical cell setup, but with two different half-cells. The working electrode is connected to the electrode pad on the probe, where the Ag / AgCl reference electrode is placed in the cathode half-cell containing HEMA (0.1 M) / EGDMA (2 wt %) / (NH4)2S2O8 (0.1 M) solution. The counter electrode is connected to a platinum pad in the anodic half-cell filled with sulfuric acid (H2SO4, 0.025 M). pHEMA deposition involves cyclic voltammetry in the range of 0 V to -0.9 V at 100 mV sec -1 The samples were rinsed with DI water after each deposition step and then dried with nitrogen.

[0052] Deployment Demonstration in a Brain Phantom

[0053] Figure 2C and Figures 5A-5B The brain phantom shown was fabricated using a custom-designed 3D-printed resin. The minimum gap between the dura mater phantom (transparent) and the pia mater phantom (light pink) is 2 mm, comparable to the distance of the actual human subdural space. To simulate the adipose tissue and connective tissue in the human subdural space with a Young's modulus of 1.6-5.5 kPa, 35 , the conductive agarose gel was injected into the gap of the phantom. The agarose gel was prepared by mixing 0.2wt% agarose powder (MB755-0500, Bio-Helix Co., Ltd) in 10× phosphate buffered saline solution (PBS, Sigma-Aldrich) and heating to 90 degrees to completely dissolve the powder. After this, the solution was injected into the gap of the phantom and then cooled at room temperature to solidify the gel. The Young's modulus of the artificial tissue gel was measured by applying a load on the cubic gel (2 cm on each side) using a tension-compression tester (Zwick Roell). As Figure 6 As shown, the load-displacement curve is converted to a stress-strain curve to fit the modulus, which is the slope of the curve.

[0054] The manipulator tips are manually manipulated. After all three manipulator tips have been navigated to the designed position, the Figure 2B and Figure 2C The lines shown are used to deploy the GD-BCI system.

[0055] In vitro electrical performance characterization

[0056] To indicate whether the microelectrodes and interconnects were damaged during the implantation and deployment process, three-point impedance measurements were performed in a brain phantom using an electrochemical workstation (Gamry Reference 600+) in 1×PBS before and after implantation.

[0057] CSC and CIC characterization were used to evaluate the electrical stimulation performance of the GD-BCI system. CSC testing was performed by three-point cyclic voltammetry in 1× PBS solution within the water electrolysis window of +0.6 V to -0.9 V using an electrochemical workstation with a scan rate of 0.1 V and a step size of 2 mV. Six cycles were performed for each measurement to stabilize the recording, and only the final recorded cycle was analyzed. CSC can be calculated using the following relationship:

[0058]

[0059] where v is the scan rate of the CV measurement, A is the area of ​​the microelectrode, i is the anodic current, and V is the scan potential.

[0060] The CIC test was performed by charge-balancing stimulation in a 1× PBS solution in a two-electrode configuration. A stimulator isolator (ISO-Flex, AMPI, Israel) controlled by a Master-9 (AMPI, Israel) was connected to the microelectrode and provided a charge-balancing current stimulation pulse with a width of 200 μs, followed by a brief pause of 50 μs and then a second reverse pulse with a width of 400 μs and an amplitude half that of the first pulse. A digital multimeter (Keithley DMM6500) was used to record the current and voltage transients. Platinum pads were used as counter and reference electrodes. The current pulse amplitude was gradually increased until the cathode or anode voltage transient exceeding the water window was observed. The CIC can be calculated using the following relationship:

[0061]

[0062] Among them I max is the maximum current pulse amplitude, t pulse is the first positive pulse width, and A is the microelectrode area.

[0063] To examine the signal quality recorded by the GD-BCI system, a typical stimulation neural signal generated by a neural signal simulator (PN-8282, Blackrock) was conducted into the conductive agarose gel inside the brain phantom via a stainless steel wire, and the GD-BCI system was also deployed into the brain phantom to detect the simulated signal. The base of the GD-BCI system was connected to a CerePlex preamplifier and a neural signal recording system (Cerebus R, Blackrock).

[0064] The electrical properties of n=4 thin film electrode arrays with a total of 1024 electrodes were characterized.

[0065] In vivo signal sensing using ECoG probes

[0066] To evaluate the performance of the guidewire-driven minimally invasive ECoG system in actual animal surgery, implantation surgery was performed on beagle dogs. With the assistance of CT images, the skull of the right hemisphere was appropriately exposed. Figures 3A-3G As shown, four skull windows with a diameter of 5 mm each were drilled to create a square shape with a side length of 35 mm, thereby ensuring that the ECoG probe can be deployed flat on the cortex. Figures 2A-2C The implantation method described in , the ECoG probe is appropriately deployed on the cortical surface including the frontal lobe, motor lobe, parietal lobe, and temporal lobe, guided by the mechanical force applied to the manipulation tip, as Figures 3A-3F To confirm the properties of the electrodes after deployment and all in vivo testing, the skull was opened to show the fully deployed device, as shown in Figure 2. Figure 3G The above results indicate that the guidewire-driven minimally invasive implantation method according to an embodiment of the present invention can be successfully performed on large animals to deploy thin-film ECoG probes onto target cortical areas and reliably achieve signal recording.

[0067] To further evaluate the performance of the ECoG probe in sensing signals over the subdural or epidural space, dogs were placed on a treadmill and connected to a CerePlex E256 preamplifier and a Cerebus neural signal processor. Figure 4 A schematic diagram shows the recording of movement-evoked event-related potential (ERP) signals from cortical areas including the frontal, motor, parietal, and temporal lobes. The recorded signals are processed and decoded by a deep learning model. Electrical stimulation can be performed on the GD-BCI to influence the animal's movements based on the decoded signals.

[0068] ECoG signal acquisition and analysis

[0069] After the ECoG probe was placed on the cortex, a CerePlex E256 preamplifier and a neural signal processor (Cerebus System, Blackrock Microsystems, USA) were connected to the probe base for signal recording. Low-pass 500 Hz and 50 Hz notch filters were applied to the raw data to filter out the ECoG signal from background noise. The filtered signal was acquired and digitized at a sampling rate of 1 kHz. Background noise level (RMS) and peak-to-peak SNR were calculated using a self-written code in Matlab.

[0070] The following are examples illustrating the process for practicing the present invention. These examples should not be considered as limiting. Unless otherwise indicated, all percentages are by weight and all solvent mixture ratios are by volume.

[0071] Example 1—Minimally Invasive Implantation and Deployment of a GD-BCI System in Vivo

[0072] The use of dogs was approved by the Ethics Committee of Guangzhou Huateng Biomedical Technology Co., LTD. (Guangdong, China). All processes were approved by the Animal Research Ethics Sub-Committee of Guangzhou Huateng Biomedical technology Co., LTD and were carried out according to the guidelines outlined in the International Laboratory Animal Assessment and Accreditation Committee (Association for Assessment and Accreditation of Laboratory Animal Care International, AAALAC). Adult male beagle dogs aged [24-26] months were used in this project. Dogs were kept under standard air humidity with a 12-hour light / dark cycle and fed WellnessComplete Health food twice daily from 10 a.m. to 11 a.m. and 5 p.m. to 6 p.m., and had free access to water throughout the experiment.

[0073] The dog was pre-anesthetized with isoflurane and placed on a stereotaxic apparatus. After the operation began, the dose of isoflurane was reduced and maintained at a level sufficient to produce analgesia without suppressing cortical electrographic activity (1.5%-2%, flow rate, anesthesia machine mode). Heart rate, blood pressure, body temperature, peripheral capillary oxygen saturation (SpO2) and end-tidal carbon dioxide (ETCO2) were monitored using an electrocardiogram monitor (BLT Q5 VET, Guangdong BiolightMeditech Co., Ltd.) throughout the operation. The skin and muscles of the right hemisphere were transected to expose the skull. Based on the canine brain atlas 36 The precise location of the target area is determined by using brain CT scan images captured before and after craniotomy. According to the size of the ECoG probe (3cm×3cm), four skull windows with a diameter of 5mm are drilled at the four corners of a 3.5cm×3.5cm square covering most of the right hemisphere to ensure the deployment of the probe. The three guide wires combined on the three corners of the ECoG probe are inserted into the same hole. Under the guidance of the mechanical force applied manually, the guide wires are manipulated out of the other three holes one by one. After all three guide wires are navigated out of the three holes, traction force (1N) is further applied to the wire to manually deploy the ECoG probe on the subdural space. The force applied to the wire is controlled by a dynamometer (Chengying Sensors Co., Ltd.). Finally, after the probe is properly deployed on the cortical surface, the traction wire is cut off. The reference end and the ground end of the probe are connected to the skull screw using silver wire.

[0074] The GD-BCI system is a minimally invasive system that can be implanted through a tiny opening in the skull. The system uses a guidewire to precisely place a dense array of electrodes over a large area of ​​the brain. These electrodes are numerous and flexible, adapting to the brain's surface to record and stimulate brain activity with high precision. Designed to treat neurological conditions and advance neuroscience research, the GD-BCI system minimizes the risks associated with traditional brain surgery, such as tissue damage and infection, making the procedure safer and more acceptable to patients.

[0075] Therefore, the GD-BCI system addresses the long-standing issues of invasiveness and safety in brain-computer interfaces. Traditional methods require large skull openings, which increase the risk of complications such as tissue damage, swelling, and infection. The GD-BCI system offers an alternative solution that facilitates extensive brain coverage and high electrode density through minimally invasive surgery, addressing the urgent need for safer and more effective brain mapping and stimulation tools in clinical and research settings.

[0076] By using a guidewire to implant a densely packed electrode array into the brain through a small millimeter-scale craniotomy, the GD-BCI system significantly reduces surgical risks compared to traditional brain surgery. 2 ) are distributed over a larger area (e.g., 9 cm 2 ) can achieve precise neural signal recording and stimulation, ensuring the safety and efficacy of brain connection.

[0077] By combining advanced electrode array design with a unique minimally invasive deployment technique, the GD-BCI system represents a significant improvement over existing brain-computer interface implantation methods. Advantages over existing solutions include reduced surgical risk, enhanced brain coverage, and increased electrode density for more accurate brain signal mapping, making it an excellent choice for neurological research and treatment, offering a safer and more effective alternative for patients and researchers.

[0078] Example 1. A guidewire-driven brain-computer interface (GD-BCI) system for minimally invasive implantation, comprising:

[0079] flexible electrode arrays; and

[0080] A plurality of flexible guide wires are attached to the flexible electrode array.

[0081] Example 2. The GD-BCI system of Example 1, wherein the flexible electrode array comprises multiple insulating parylene-C layers, metal interconnects, and electrodes made of PEDOT:PSS / pHEMA and gold.

[0082] Embodiment 3. The GD-BCI system according to embodiment 1, wherein adjacent metal interconnects are spaced apart by a distance of 10 μm.

[0083] Embodiment 4. The GD-BCI system of embodiment 2, wherein the metal interconnects are formed of gold and are fully encapsulated between adjacent insulating Parylene-C layers.

[0084] Example 5. The GD-BCI system according to Example 1, wherein the density of the flexible electrode array is 28.4 electrodes cm -2 .

[0085] Example 6. The GD-BCI system of Example 1, wherein the plurality of flexible guidewires have three manipulation tips.

[0086] Example 7. The GD-BCI system according to Example 1, wherein the multiple flexible guide wires are configured to be guided by an external mechanical force so that the flexible electrode array passes through the craniotomy area and is deployed by tracking multiple manipulation tips.

[0087] Example 8. A GD-BCI system according to Example 1, wherein the flexible electrode array is formed of a biocompatible material, and the biocompatible material comprises one or any one of poly(p-xylene-C), poly(2-hydroxyethyl methacrylate) (pHEMA), polydimethylsiloxane (PDMS) and polyvinyl acid (PGA).

[0088] Example 9. The GD-BCI system according to Example 1, wherein the flexible electrode array comprises 256 microelectrodes.

[0089] Embodiment 10. The GD-BCI system of embodiment 2, wherein each of the plurality of insulating parylene-C layers comprises a plurality of perfusion holes.

[0090] Embodiment 11. The GD-BCI system of embodiment 2, wherein the plurality of flexible guidewires are attached to corner sections of the parylene-C layer of the flexible electrode array.

[0091] Example 12. The GD-BCI system of Example 1, wherein each of the plurality of flexible guidewires comprises a steering tip and a pull wire.

[0092] Example 13. The GD-BCI system according to Example 12, wherein the traction wire is an absorbable surgical suture made of polyvinyl acid (PGA) and can be absorbed by the human body.

[0093] Example 14. A method for deploying a guidewire-driven brain-computer interface (GD-BCI) system for minimally invasive implantation in an individual, comprising:

[0094] Obtaining the GD-BCI system according to Example 1;

[0095] guiding the plurality of flexible guidewires of the GD-BCI system; and

[0096] The flexible electrode array of the GD-BCI system is positioned within the subdural or epidural space of a subject.

[0097] Example 15. The method of Example 14, wherein the guidewire is individually manually controlled through a first opening in the subject and exits through a second opening in the subject.

[0098] Example 16. The method according to Example 15, wherein when the pull wires of the guide wire are respectively led out from three openings, the flexible electrode array is positioned by pulling the pull wires.

[0099] Example 17. A method according to Example 14, wherein, when the flexible electrode array of the GD-BCI system is positioned within the epidural space of an individual, the GD-BCI system is configured to generate a frequency spectrum indicating different levels of alpha / beta band (e.g., 10 to 30 Hz) and gamma 1 band (e.g., 30 to 50 Hz) power in the individual during wakefulness and sleep.

[0100] Embodiment 18. The method of embodiment 17, wherein the alpha / beta band is in the range between 10 and 30 Hz.

[0101] Embodiment 19. The method of embodiment 17, wherein the γ1 band is in the range between 30 and 50 Hz.

[0102] All patents, patent applications, provisional applications, and publications mentioned or cited herein are hereby incorporated by reference in their entirety, including all figures and tables, to the extent not inconsistent with the explicit teachings of this specification.

[0103] It should be understood that the examples and embodiments described herein are for illustrative purposes only, and that various modifications or variations made in accordance with these examples and embodiments will be suggested to those skilled in the art and will be included within the spirit and scope of this application. Additionally, any element or limitation of any invention disclosed herein or its embodiments may be combined with any and / or all other elements or limitations (individually or in any combination) or any other invention or embodiment disclosed herein, and all such combinations are intended without limitation with respect to the scope of the invention.

[0104] References

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Claims

1. A guidewire-driven brain-computer interface (GD-BCI) system for minimally invasive implantation, characterized in that: include: flexible electrode arrays; as well as A plurality of flexible guide wires are attached to the flexible electrode array.

2. The GD-BCI system according to claim 1, characterized in that The flexible electrode array includes multiple insulating parylene-C layers, metal interconnects, and electrodes made of PEDOT:PSS / pHEMA and gold.

3. The GD-BCI system according to claim 1, characterized in that Adjacent metal interconnect lines are spaced apart by a distance of 10 μm.

4. The GD-BCI system according to claim 2, characterized in that The metal interconnects are formed of gold and are fully encapsulated between adjacent insulating Parylene-C layers.

5. The GD-BCI system according to claim 1, characterized in that The density of the flexible electrode array is 28.4 electrodes cm -2 .

6. The GD-BCI system according to claim 1, characterized in that The plurality of flexible guidewires have three steering tips.

7. The GD-BCI system according to claim 1, characterized in that The plurality of flexible guidewires are configured to be guided by an external mechanical force so that the flexible electrode array passes through a craniotomy area and is deployed by tracking a plurality of manipulation tips.

8. The GD-BCI system according to claim 1, characterized in that The flexible electrode array is formed of a biocompatible material, and the biocompatible material includes one or any one of parylene-C, poly(2-hydroxyethyl methacrylate) (pHEMA), polydimethylsiloxane (PDMS) and polyvinyl acid (PGA).

9. The GD-BCI system according to claim 1, characterized in that: The flexible electrode array includes 256 microelectrodes.

10. The GD-BCI system according to claim 2, characterized in that: Each of the plurality of insulating Parylene-C layers includes a plurality of potting holes.

11. The GD-BCI system according to claim 2, characterized in that: The plurality of flexible guidewires are attached to corner sections of the parylene-C layer of the flexible electrode array.

12. The GD-BCI system according to claim 1, characterized in that Each of the plurality of flexible guidewires includes a steering tip and a pull wire.

13. The GD-BCI system according to claim 12, characterized in that: The traction thread is an absorbable surgical suture made of polyvinyl acid (PGA) and can be absorbed by the human body.

14. A method for deploying a guidewire-driven brain-computer interface (GD-BCI) system for minimally invasive implantation in an individual, characterized in that: The method comprises: Obtaining the GD-BCI system according to claim 1; guiding the plurality of flexible guidewires of the GD-BCI system; and The flexible electrode array of the GD-BCI system is positioned within the subdural or epidural space of a subject.

15. The method according to claim 14, characterized in that The guidewire is individually manually controlled through a first opening in the subject and exits through a second opening in the subject.

16. The method according to claim 15, characterized in that Each of the plurality of flexible guidewires includes a steering tip and a pull wire.

17. The method according to claim 16, characterized in that When the pull wire of the guide wire is led out from the second opening, the flexible electrode array is positioned by pulling the pull wire.

18. The method according to claim 14, characterized in that When the flexible electrode array of the GD-BCI system is positioned within the epidural space of an individual, the GD-BCI system is configured to generate a frequency spectrum indicating different levels of alpha / beta band and gamma 1 band power during wakefulness and sleep in the individual.

19. The method according to claim 18, characterized in that The alpha / beta band is in the range between 10 and 30 Hz.

20. The method according to claim 18, wherein The γ1 band is in the range between 30 and 50 Hz.

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