Micro-electrode stitch device for monitoring of brain activity

Abstract

The disclosed embodiments relate to devices, systems, and methods that, among other features and benefits, provide a robust alternative to scalp electroencephalogram (EEG) electrodes that can be quickly applied, require no upkeep, enable high-fidelity EEG recordings, and can be implemented in various settings. An example device for monitoring brain activity includes a plurality of wires including a plurality of electrodes configured to obtain EEG signals associated with different regions of a scalp, the plurality of electrodes configured to be threaded into a skin layer beneath a surface of the scalp using the plurality of wires to enable positioning of the plurality of electrodes within the skin layer at the different regions.

Description

PCT Patent Application Attorney Docket No. 009062.8590.WO00MICRO-ELECTRODE STITCH DEVICE FOR MONITORING OF BRAIN ACTIVITYSTATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0001] This invention was made with government support under NS 123723, NS 123655 and EB029757 awarded by the National Institutes of Health. This invention was also made with funding from Air Force Office of Scientific Research, Department of Defense with grant number FA9550-22-1-0454. The government has certain rights in the invention.CROSS-REFERENCE TO RELATED APPLICATION

[0002] This patent document claims priority to and benefits of U.S. Provisional Application, 63,777,341, entitled “MICRO-ELECTRODE STITCH DEVICE FOR MONITORING OF BRAIN ACTIVITY”, and filed on March 25, 2025. The entire content of the above identified patent application is incorporated by reference as part of the disclosure of this patent document.TECHNICAL FIELD

[0003] The present disclosure is generally directed to systems, methods, and devices for monitoring brain activity using engineered electrodes.BACKGROUND

[0004] Electroencephalogram (EEG) is a non-invasive neurophysiological monitoring technique that records electrical activity in the brain through electrodes placed on the scalp. It captures brainwave patterns that reflect the brain’s electrical signals, providing valuable information about brain activity. EEG is widely used in clinical settings for diagnosing neurological disorders, as well as in research to study brain function and cognitive processes. Long-term EEG monitoring, which is often necessary to detect abnormal brain activity, capture seizures, and characterize epilepsy, has been difficult to sustain for both patients and providers and is limited to the clinical setting. Currently, patients have electrodes placed on their scalp with an adhesive, which often can lead to skin irritation, skin breakdown, discomfort, and even scarring; sweat, patient movement, and necessary clinical care can all lead to poorly connected electrodes. As a result, those underlying brain locations are not completely recorded and could lead to missed epilepsy diagnoses. Therefore, there is a need for a system that allows quick, 009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00minimally invasive placement of EEG electrodes with minimal patient discomfort, while enabling sustained and robust multi -day recordings within and outside of the clinical setting.SUMMARY

[0005] The disclosed embodiments relate to devices, systems, and methods that, among other features and benefits, provide a robust alternative to scalp EEG electrodes that can be quickly applied, require no upkeep, and enable high-fidelity EEG recordings.BRIEF DESCRIPTION OF THE DRAWINGS

[0006] FIGS. 1A-1B shows drawings and images of an example embodiment and implementation of a NeuroWeave device.

[0007] FIG. 2 shows a three-dimensional view of an example embodiment of a NeuroWeave device.

[0008] FIG. 3A shows a 2-D schematic of a NeuroWeave epidermal placement according to an example embodiment.

[0009] FIG. 3B shows a 3-D schematic of a NeuroWeave threading process of the upper skin layer according to an example embodiment.

[0010] FIG. 4 shows an image of a wired NeuroWeave device with sterilizable connectors according to an example embodiment.

[0011] FIG. 5 shows a schematic illustrating steps in a photolithography process according to an example embodiment.

[0012] FIG. 6 shows a flowchart of steps in a microfabrication process according to an example embodiment.

[0013] FIG. 7 shows a schematic illustrating steps in a fabrication process according to an example embodiment.

[0014] FIG. 8 shows a flowchart of steps in a microfabrication process according to an example embodiment.

[0015] FIG. 9 shows a flowchart of steps in a microfabrication process according to an example embodiment.

[0016] FIG. 10 A shows an image of a wearable wireless device according to an example embodiment.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0017] FIG. 10B shows an image of an interior part of a wearable wireless device according to an example embodiment.

[0018] FIG. 10C shows an image of a magnetic attachment of rechargeable batteries to a wearable wireless device according to an example embodiment.

[0019] FIG. 10D shows a block diagram of a wireless system according to an example embodiment.

[0020] FIGS. 11A-C show images of some NeuroWeave threads in accordance with example embodiments.

[0021] FIG. HD shows example electrochemical impedance spectra of a NeuroWeave thread without a poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) coating in accordance with an example embodiment.

[0022] FIGS. 1 IE-1 IF show example electrochemical impedance spectra of NeuroWeave threads with and without PEDOT:PSS coating and relative impedance magnitude at 1kHz frequency.

[0023] FIGS. 12A-12D show example results obtained in a demonstration of a NeuroWeave device.

[0024] FIG. 13 shows example results obtained in a demonstration of a NeuroWeave device and images showing placement of the NeuroWeave device in a human subject in accordance with disclosed techniques.

[0025] FIG. 14 shows an image of an example embodiment of the NeuroWeave.

[0026] FIG. 15 shows a block diagram illustrating an example embodiment of a data processing unit that can be included or implemented with the example embodiments of the NeuroWeave device.

[0027] FIGS. 16A-J shows example illustrations, images, and data plots related to some disclosed embodiments of the NeuroWeave.

[0028] FIGS. 17A-17L show example illustrations, images, and data plots related to a demonstration of an example embodiment of the NeuroWeave.

[0029] FIGS. 18A-18N show example illustrations, images, and data plots related to a demonstration of an example embodiment of the NeuroWeave.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0030] FIGS. 19A-19N show example illustrations, images, and data plots related to a demonstration of an example embodiment of the NeuroWeave.DETAILED DESCRIPTION

[0031] Recent advances in electrode technology have focused on using biocompatible polymers to achieve conformal coverage on uneven skin surfaces. However, existing research primarily concentrates on soft epidermal platforms, which suffer from reliability issues, attenuated bioelectronic signatures, and detachment over time. Alternative technologies like subscalp EEG (ssEEG) aim to enhance diagnostic yield by extending recording durations with high signal quality. Yet, ssEEG platforms (e.g., Neuroview™, Epios™, EASEE™, EpiMinder and UNEEG™) require incisions between the scalp and skull of at least 1 cm, leading to limited spatial coverage and reduced tolerability due to contraindications (e.g., fractures or hematomas). The trade-off between these electrode technologies revolves around signal quality versus invasiveness, necessitating innovative recording schemes to alleviate patient burdens.

[0032] The present patent document discloses, among other things, devices, systems, and methods that provide a robust alternative to scalp EEG electrodes that can be quickly applied, require no upkeep, and enable high-fidelity EEG recordings. An example device includes an ultra-thin thread-based electrode stitch with spatially controlled contact spacing for clinical recording of electroencephalographic signatures.

[0033] Disclosed are devices, systems and methods that include ultra-thin thread-based electrodes with spatially controlled contact spacing, in accordance with the present technology, which can be used for clinical recording of electroencephalographic signatures, referred to as “NeuroWeave.” The disclosed embodiments use engineered electrodes to enable recording of EEG data.

[0034] In an example embodiment, NeuroWeave is embodied as a miniaturized, scalable device comprising at least four bundled ultra-thin wires / threads into a single “weave” capable of minimally invasively stitching onto scalp tissue for electrophysiological recording as a combined “weave ’’ / wire from anterior to posterior across the skull. Attached to a medical needle or deployed via injection, the NeuroWeave features dimensions similar to conventional sutures (e.g., 100 - 300 pm), reducing tissue damage and patient discomfort near surgical sites. Furthermore, reconfigurable contacts can be functionalized, roughened, coated, or electrodeposited with materials that can improve physiological sampling and neurophysiological009062.8590. WO00M86161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00recordings. As an example, PEDOT:PSS can be electrodeposited on the surface of a conductive portion of the NeuroWeave to ensure low electrochemical impedances and high signal quality. This device introduces a new design approach for reliably measuring relevant electrophysiological signatures to monitor patient recovery.

[0035] In some embodiments, the NeuroWeave is used as a monitoring device to measure brain activity and is positioned under the skin to allow for a robust, longer-term recording in comparison to scalp EEG electrodes. The NeuroWeave electrodes offer higher quality signals than can be obtained with conventional scalp electrodes. The disclosed device allows for minimally invasive, high fidelity recording of brain activity in a manner which minimizes patient discomfort or risk.

[0036] The disclosed embodiments can be implemented in various applications, including those in which scalp EEG recordings are typically employed. Example applications of the disclosed technology include monitoring brain activity to diagnose and manage seizures, coma, sleep states, medication use and effectiveness, operative interventions, delirium, psychiatric disease or any other condition in which scalp EEG is indicated, as well as brain-computer interfaces.

[0037] For example, NeuroWeave can be used as an acute or semi-chronic device (e.g., <30 days) for monitoring of brain activity in the outpatient clinic, the intensive care unit (ICU), the epilepsy monitoring unit (EMU) or any other location in the hospital. NeuroWeave can also be deployed for use as a semi-chronic or even long-term (chronic) recording system of brain activity in the home setting as well. Additionally, NeuroWeave can be used as a post-operative monitoring device to measure EEG activity from patients recovering from epilepsy and brain tumor surgeries. The NeuroWeave can mediate the process of post-surgical evaluation of brain activity eliminating the need for contact surface electrodes on surgical sites. The NeuroWeave can be used as a semi-chronic device (e.g., <30 days) or at home-monitoring device that is minimally invasive reducing patient discomfort and prolonged Epilepsy Monitoring Unit (EMU) visit. The NeuroWeave can also be used for monitoring any type of brain activity from the scalp, for example, record brain activity to enable objective, continuous monitoring of biomarkers associated with medication adherence and therapeutic response. In some embodiments, the p-electrodes of NeuroWeave can offer higher quality of signals with access to the interstitial fluid that is not attainable with epidermal electrodes. The extracted signals can be used to monitor recovery and provide holistic view of electrophysiological and metabolic activity.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0038] In addition to human clinical use, NeuroWeave can be integrated in pet remote / wireless health-monitoring systems. This integration can enable direct measurement of biomarkers, health conditions, or emotional states of pets that is not possible otherwise. It is also possible for NeuroWeave to be used for electrical stimulation and therefore in herding conditions for animals.

[0039] NeuroWeave is a versatile and flexible-for-use device that can improve existing clinical monitoring and provide opportunities for better care of humans and animals.

[0040] The disclosed embodiments include devices, systems, and methods that use ultrathin thread-based electrodes that can be bundled and stitched into the epidermis, or injected beneath the dermis, for minimally invasive, long-term, robust, high-fidelity monitoring of brain activity with minimal discomfort. In some example applications, patients could have these electrodes placed for up to 30 days with minimal upkeep.

[0041] FIG. 1A shows drawings demonstrating an example implementation of an embodiment of the NeuroWeave. In FIG. 1 A (left), the electrodes of the NeuroWeave are located within the region represented using the rectangular inset box and are shown relative to typical scalp recording electrodes to provide a sense of scale. FIG. 1A (right) depicts how the NeuroWeave electrodes can be stitched to the scalp, emphasizing the minimally invasive, ambulatory, and comfortable nature of the approach, for example, using 5 gold NeuroWeave threads. FIG. IB (top) shows an example scanning electron microscopy (SEM) image of a single NeuroWeave thread with unidirectional etch of an insulation layer. As shown in FIG. IB (top), some embodiments of NeuroWeave include an electrically conductive inner portion (e.g., comprising Au) which is at least partially covered by an insulation layer which can be etched to form electrodes configured to obtain EEG signals. FIG. IB (bottom) shows a picture of an example single NeuroWeave thread on a fingertip, demonstrating that is thinner than a human hair.

[0042] FIG. 2 shows an example embodiment of a three-dimensional NeuroWeave device 200. The device 200 includes multiple gold wires or threads 201. Each wire 201 has a diameter of at least ~40 pm and is coated with an insulation layer 202 comprising polyimide. Polyimide is a common biocompatible and flexible material that is used for neural probes. The total thickness of the insulation layer 202 is ~5 - 10 pm. The device 200 includes contact electrodes 203 formed by etching a portion of the insulation layer 202 using microfabrication techniques to expose part of the gold wire 201. The contact electrodes 203 are then electrodeposited with009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00PEDOT:PSS 204. PEDOT:PSS is also a biocompatible conductive polymer that is used to lower the impedances for better signal quality during recording. As shown in FIG. 2, the wires 201 are twisted together to allow spatial control of the contact electrodes 203 (e.g., 1 cm spacing). For signal acquisition, connections 205 are also etched during the microfabrication process exposing part of the gold wires 201 on the surface. The connections 205 are reconfigurable (e.g., 0.2 - 2 cm) depending on the length of the device 200 and number of contacts 203 required. The bundled wires 201 can be coupled to a tool (e.g., knotted on a medical needle 206) for conventional suturing on skin tissue. In some embodiments, the contacts 203 and connections 205 are 1 mm and 1 cm wide, respectively. In some embodiments, the connections 205 are connected to a potentiostat or touch-proof connectors using conductive paste. In some embodiments, at least some of the contact electrodes 203 include a surface modification or a coating that can lower the impedance of the contact electrode 203.

[0043] FIG. 3A shows a 2-D schematic of an example NeuroWeave epidermal placement in comparison to other electrode technologies such as scalp EEG, electrocochleography (ECoG), and intracortical microelectrodes. FIG. 3B shows a 3-D schematic illustrating an example NeuroWeave threading process of the upper skin layer compared to scalp EEG that requires gel adhesive for placement. The NeuroWeave connections can be connected to a potentiostat or touch-proof connectors using conductive paste (unpictured).

[0044] FIG. 4 shows an image of an example embodiment of a NeuroWeave device (e.g., device 200) soldered to connectors. In FIG. 4, the NeuroWeave device 401 is connected to clinical touch proof connectors 402.

[0045] FIG. 5 shows a schematic illustrating steps in an example photolithography process which can be used in fabrication of some disclosed embodiments. In FIG.5, the left hand column shows schematic of an example wafer used in the fabrication at a respective step in the fabrication process and the right hand column shows a cross-sectional view of the wafer at the respective step in the fabrication process.

[0046] Referring to FIG. 5, at step 510, photoresist (e.g., SU-8 2005) is spun-casted on a 4-in silicon wafer 501. Any size of wafer can be used. SU-8 2005 is patterned by photolithography into a pattern with width of -65 pm and length of 8 cm. As shown in FIG. 5, patterning of the wafer 501 provides trenches 502 to place the gold wires. The length of a trench 502 can be customized. At step 520, insulated gold wires 503 and 504 are cut to 8 cm length from a spool and placed onto a 6-inch glass plate. Gentle finger pressing on the wire 503 and / or009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00504 and applying isopropyl alcohol (IP A) allows straightening by rolling motion. The wires 503 and 504 are then placed onto trenches 502. At step 530, a 4-inch glass wafer 506 is spun-casted with thick positive photoresist (e.g., -12 - 14 pm) 505. Any size of wafer can be used. The positive photoresist 505 is semi -cured at 110°C for 22 s. Then, the glass wafer 506 with semicured photoresist 505 is placed on top of the silicon wafer 501 with the wires 503 and 504. To ensure alignment of the wafers 501 and 506 during the stamping process, at step 540, a customized 3D-printed wafer carrier 507 is used to place the silicon wafer 501 on bottom. At step 550, the carrier 507 with the sandwiched wafers 501 and 506 is transferred to convective oven at ~105°C for 1:40 min. Afterwards, the wafers 501 and 506 are cooled down before detaching the silicon wafer 501 as shown in step 560. Detaching the wafers 501 and 506 allows transferring the wires 503 and 504 to the semi-cured adhesive photoresist 505. The glass wafer 506 with the transferred wires 503 and 504 is then placed on a hot plate at 110°C for 1 min to ensure fully cured photoresist 505. At step 570, another layer of positive photoresist 505 is spun-casted on top of the wires 503 and 504. The double-coated wafer 506 is then cured at 110°C for at least 15 min to ensure evaporation of all residual solvent. At step 580, a photolithography process patterns the connections 509 and contacts 509 on the length of the wires 503 and 504. An etching process with oxygen and tetrafluoromethane gases for 30 min - 40 min selectively removes the polyimide insulation of the wires 503 and 504 on the exposed areas 508 and 509. To prevent foaming effect, the wafer 506 can be flood exposed for 3 s before etching process. Also, to reduce microcracking of thick photoresist, the etching process can be done in 5 minute segments to allow cooling of the wafer 506.

[0047] FIG. 6 shows a flowchart of steps in an example microfabrication process flow in accordance with some disclosed embodiments. Referring to FIG. 6, at step 601, the process includes patterning trenches onto a 4-in silicon wafer with photoresist. At step 602, gold wires from a spool are cut into 8 cm lengths and placed on a 6-in glass plate. At step 603, IPA and gentle rolling motion allows straightening of the insulated wires. At step 604, the wires are transferred onto the trenches. At step 605, a thick positive photoresist is spun-casted on a 4-inch glass wafer. At step 606, the wafer is placed on a hot plate at 110°C for 22 s for adhesiveness. At step 607, the silicon wafer holding the wires is placed on top of a 3D-printed wafer carrier for alignment. At step 608, the semi-cured glass wafer is removed from the hot plate and stamped on top of the silicon wafer. At step 609, the wafer carrier is placed in an oven at ~ 105°C for 1:40 min. At step 610, after cooling, the wafers can be detached to realize the transferred gold wires onto the glass wafer. At step 611, subsequent curing of the glass wafer with wires on 009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00top at 110°C for 1 min ensures fully cured photoresist. At step 612, a second layer of photoresist is spun-casted and cured at 110°C for at least 15 min to ensure evaporation of residual solvent. At step 613, a photolithography process exposes the contacts (e.g., 1 mm) and connections (e.g., 1 cm) of the wires sandwiched between the photoresist. At step 614, flood exposure for 3 s prevents foaming effect during etching process. At step 615, dry etching with oxygen and tetrafluoromethane gases for 30 - 40 min in 5 min segments prevents cracking of thick photoresist and selectively removes polyimide insulation at predetermined locations. At step 616, the wafer is retrieved, and copper wires with conductive paste are added onto the connection sections to analyze the electrochemical impedance spectroscopy (EIS) in a phosphate buffered saline solution with Ag / AgCl reference electrode and Pt wire counter electrode. At step 617, electrodeposition of PEDOT:PSS is performed on each contact and EIS is measured again before sterilization and deployment for medical use. At step 618, to retrieve the wires from the wafer, the photoresist is dissolved in an acetone bath. At step 619, the wires with different contact spacings are bundled semi-manually by twisting motion through custom-made roller. At least 5mm on both ends of the device are kept untwisted for subsequent data acquisition connections. At step 620, for mechanical fixation of the bundled wires, medical UV adhesive based on acrylate ester can be used on the needle end of the knot.

[0048] FIG. 7 shows a schematic illustrating steps in an example shadow mask process which can be used in fabrication of some disclosed embodiments At step 710, predefined cut thermal release tape is placed on a 6-in silicon wafer 701. The thermal release tape 702 on the wafer 701 are adhesive sites to place the gold wires 703. The length of the thermal release tape 702 can be altered. Insulated gold wires 703 are cut to 16 cm length from a spool and placed onto a 6-inch glass plate. Gentle finger pressing on the wire and applying isopropyl alcohol (IP A) allows straightening by rolling motion. At step 720, the wires 703 are then placed onto trenches 703. At step 730, a customizable metallic shadow mask is gently placed above to expose the contacts 703 and connections 704. At step 740, an etching process with oxygen and tetrafluoromethane gases for 30 min - 40 min selectively removes the polyimide insulation on the exposed areas 705.

[0049] FIG. 8 shows a flow chart of steps in an example microfabrication process flow in accordance with some disclosed embodiments. At step 801, the process includes cutting thermal release tapes onto a 6-in silicon wafer. At step 802, gold wires from a spool are cut into 16 cm lengths and placed on a 6-in glass plate. At step 803, IPA and gentle rolling motion allows straightening of the insulated wires. The wires are placed on the predefined cut thermal release 009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00tape. At step 804, a customizable shadow mask is gently placed above the wafer. At step 805, dry etching with oxygen and tetrafluoromethane gases for 30 - 40 min selectively removes polyimide insulation at desired locations. At step 806, to retrieve the wires from the wafer, the thermal release tape is heated under a hot plate at 120 C for at least two minutes. At step 807, after removing the threads from the thermal release tape, copper wires with conductive paste are added onto the connection sections to analyze the electrochemical impedance spectroscopy (EIS) in a phosphate buffered saline solution with Ag / AgCl reference electrode and Pt wire counter electrode. At step 808, electrodeposition of PEDOT:PSS is performed on each contact and ETS is measured again before sterilization and deployment for medical use. At step 809, the wires with different contact spacings are bundled semi-manually by twisting motion through custom-made roller. At least 5mm on both ends of the device are kept untwisted for subsequent data acquisition connections. At step 810, for mechanical fixation of the bundled wires, medical UV adhesive based on acrylate ester can be used on the needle end of the knot.

[0050] FIG. 9 shows a flow chart of steps in an example fabrication method to enhance the adhesion of the PEDOT:PSS to gold by chemically binding a cross-linker (3-Glycidyloxypropyl)Trimethoxysilane (GOPS) to the PSS chains in accordance with some disclosed embodiments. At step 901, the adhesion between PEDOT:PSS and gold is mediated by functionalizing the surface with hydroxyl groups such as 11 -Mercapto- 1 -undecanol. At step 902, rinsing in ethanol removes the excess material. At step 903, the hydroxyl groups immobilized on the surface cross-link with GOPS via solution deposition to allow chemical anchoring on the gold surface. At step 904, rinsing before electrodeposition removes the uncross linked GOPS. At step 905, electrodeposition of PEDOT:PSS on the surface enables further cross-linking of the PSS chains into the GOPS.

[0051] FIGS. 10A-10C show images of an example embodiment of a wireless NeuroWeave system 1000. Specifically, FIG. 10A shows components of the NeuroWeave wireless system 1000 which comprises a wireless module 1001, rechargeable battery pack 1002 with 190mAh LiPo battery, and NeuroWeave electrodes 1004 (e.g., electrodes of a device such as device 200, 401) with a customized FPC cable 1003. As shown in FIG. 10B, the wireless module 1001 comprises a wireless circuit 1005 which comprises chip components including microprocessors, power regulator, low-power Bluetooth module, FPC connector 1006 for interfacing with the NeuroWeave electrodes 1004, and magnetic connectors 1007 for battery connection. All components are mounted using a reflow soldering process at the designated locations. Both the wireless module 1001 and battery pack 1002 feature conductive magnetic 009062.8590. WO00M86161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00connectors 1007, allowing for easy plug-in power connection between the wireless module 1001 and the battery pack 1002 as shown in FIG. 10C. In some implementations, a rechargeable Lithium-ion Polymer (LiPo) battery provides up to 10 hours of continuous operation, enabling uninterrupted EEG signal monitoring. FIG. 10D shows a diagram illustrating an example operation of the wireless system 1000. As shown in FIG. 10D, in some embodiments, the system 1000 features a multichannel differential amplifier and a Bluetooth Low Energy (BLE) microcontroller with a 2.4 GHz antenna. In some embodiments, a connected client device records and plots the measured data in real time.

[0052] FIGS. 11A-11F show example results and images obtained from bench-top, animal, and human testing of some embodiments of the NeuroWeave that demonstrate functionality of the disclosed technology. FIG. 11 A shows a photographic image of an example of 8 cm bundled wires. Inset of FIG. 11A shows the twisted wires. FIG. 11B (left) shows an image of an example NeuroWeave electrode. FIG. 11B shows an optical microscopic image of the electrodeposited contact. FIG. 11C shows the benchtop impedances after etching process. FIG. 1 ID and FIG. 1 IE show benchtop impedance after electrodeposition of 1 mm contact and the comparison at 1 kHz, respectively. FIG. 11F shows a scanning electron microscopy image of the etched electrode.

[0053] Example implementations of some embodiments of a NeuroWeave device were conducted in animal tests. Acute cases were performed to measure EEG signals compared to conventional screw electrodes. FIG. 12A shows example baseline activity data of the NeuroWeave when compared to a control screw electrode. In addition, the electrochemical impedance was measured and the signal-to-noise ratio (SNR) computed as depicted in FIG. 12B . In addition, whisker barrel stimulation was performed at different frequencies of air puff to record somatosensory evoked potentials (SSEPs) as shown in FIG. 12C. Moreover, FIG. 12D shows SSEPs of electrically stimulating the forelimb and hindlimb when compared to a control electrode.

[0054] For early human testing, preliminary testing in a healthy control was performed using an example NeuroWeave device. Example results of the test and placement of the NeuroWeave device are shown in FIG. 13. FIG. 13 demonstrates the ability to get a posterior dominant rhythm, a normal and characteristic finding of scalp EEG. There were no issues with the placement with minimal blood and discomfort, and we were able to demonstrate a robust recording to movement and sweat over the course of 2 hours.009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0055] In some embodiments, a NeuroWeave device or system is implantable. FIG. 14 shows an image of an example NeuroWeave device (~ 16 cm length) connected to a clinical touch proof connector to record EEG on patients. FIG. 14 shows a miniaturized printed circuit board (PCB) is assembled in between the NeuroWeave device and the clinical touch-proof connector for additional mechanical strength during handling.

[0056] FIG. 15 shows a block diagram illustrating an example embodiment of a data processing unit that can be included or implemented with the example embodiments of the NeuroWeave device. The data processing unit can include a processor 121 that can be in communication with a memory unit 122, an input / output (I / O) unit 123, and / or an (optional) output unit 124.

[0057] The processor 121 is configured to process data, and the memory unit 122 is in communication with the processor 121 to store and / or buffer the data. To support various functions of the data processing device unit, the processor 121 can be included to interface with and control operations of other components of the NeuroWeave device, such as via the I / O unit 123 and / or the (optional) output unit 124. The processor 121 can include one or more processors, e.g., including but not limited to microprocessors such as a central processing unit (CPU), microcontrollers, or the like.

[0058] The memory unit 122 can include and store processor-executable code, which when executed by the processor, configures the data processing unit to perform various operations, e.g., such as receiving information, commands, and / or data, processing information and data, and transmitting or providing information / data to another device. The memory unit 122 can store other information and data, such as instructions, software, values, images, and other data processed or referenced by processor 121. For example, various types of Random Access Memory (RAM) devices, Read Only Memory (ROM) devices, Flash Memory devices, and other suitable storage media can be used to implement storage functions of memory unit 122. The memory unit 122 can store data and information, which can include subject EEG data, NeuroWeave device and / or system parameters, data processing parameters, and processed parameters and data that can be used in the implementation of data processing techniques, e.g., techniques in accordance with the disclosed technology. The memory unit 122 can store data and information that can be used to implement an EEG signal acquisition and / or characterization method, e.g., including one or more algorithms for implementing an EEG method, and store data009062.8590. WO00M86161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00and information that can be generated from an algorithm and / or model of the EEG-based protocol in accordance with the disclosed technology.

[0059] In some implementations, the data processing unit includes an input / output unit (I / O) 123 to interface the processor 121 and / or memory unit 122 to other modules, units or devices associated with the system 100, and / or external devices. The I / O unit 123 can connect to an external interface, source of data storage, or display device. Various types of wired or wireless interfaces compatible with typical data communication standards, such as Universal Serial Bus (USB), IEEE 1394 (FireWire), Bluetooth, Bluetooth low energy (BLE), ZigBee, IEEE 802.11, Wireless Local Area Network (WLAN), Wireless Personal Area Network (WPAN), Wireless Wide Area Network (WWAN), WiMAX, IEEE 802.16 (Worldwide Interoperability for Microwave Access (WiMAX)), 3G / 4G / LTE / 5G / 6G cellular communication methods, and parallel interfaces, can be used to implement I / O unit 123. In some implementations, for example, the data processing unit includes a wireless communications unit, e.g., such as a transmitter (Tx) or a transmitter / receiver (Tx / Rx) unit. The I / O unit 123 can interface the processor 121 and memory unit 122 with the wireless communications unit to utilize various types of wireless interfaces, such as the examples described above. The I / O unit 123 can interface with other external interfaces, sources of data storage, and / or visual or audio display devices, etc. to retrieve and transfer data and information that can be processed by the processor 121, stored in the memory unit 122, or exhibited on an output unit of a user device (e.g., display screen of a computing device) or an external device.

[0060] To support various functions of the data processing unit, the data processing unit may optionally include an output unit 124 that can be used to exhibit data implemented by the example NeuroWeave device. The (optional) output unit 124 can include various types of display, speaker, or printing interfaces to implement output functionalities the system 100. In some embodiments, for example, the (optional) output unit 124 can include cathode ray tube (CRT), light emitting diode (LED), or liquid crystal display (LCD) monitor or screen as a visual display. In some examples, the (optional) output unit 124 can include toner, liquid inkjet, solid ink, dye sublimation, inkless (such as thermal or UV) printing apparatuses to implement some output modalities of the (optional) output unit 124. In some examples, the (optional) output unit 124 can include various types of audio signal transducer apparatuses.

[0061] In some embodiments, a bundle of ultra-thin insulated Au wires (50 pm each -insulation of 10 pm and conductor of 40 pm) have sections along the length that are etched for009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00recording and data acquisition. The additional elements in the fabrication process enables high throughput and yield of electrodes with customizable features (0.25 - 10 mm openings). These elements exploit (1) placing thin wires on developed trenches on a small or a larger Si or glass wafer (101.6 or 152.4 mm). This wafer contains at least eight trenches (65 pm width each) to allow multiple wires to be placed on. (2) The Si or glass wafer with aligned wires is transferred to another semi-cured wafer coated with photoresist by stamping. Detaching the two wafers enables seamless transfer of the insulated wires for subsequent microfabrication steps.

[0062] In addition, another fabrication technique can be exploited for rapid microfabrication process with high throughput and yield. These elements exploit (1) placing thin wires on thermal release tape on a customizable Si or glass wafer (101.6 - 200 mm). This wafer contains a range of thermal release tapes from 1 - 20 to allow multiple wires to be adhered on. (2) A customizable metal shadow mask is placed on the adhered wires on a Si or glass wafer for subsequent microfabrication steps. Therefore, leveraging these techniques allows flexibility in the design and scalability in the production of p-electrodes. Assembling the p-electrodes with controlled contact spacing and threading it to a medical needle enables enough incision force for stitching it on the epidermis. Moreover, the bundled electrodes can be deployed beneath the skin through a small incision via injection.

[0063] Example embodiments of the NeuroWeave devices, systems, and methods utilize ultra-thin thread-based electrodes that can be bundled and stitched into the epidermis for minimally invasive monitoring of brain activity. Various benefits and aspects of some example embodiments of the disclosed technology include the following.

[0064] 1) Scalable fabrication and flexibility in the design of the thread-based stitch: p-electrodes (e.g., length up to 20 cm) can be tailored to custom-based application accommodating clinical needs. The length of the contact (e.g., 0.25 - 10 mm) its spacing (e.g., 0.5 mm - 30 mm) can be further reduced or extended owing to the scalable and reproducible microfabrication process. The alteration in design can be mass produced cost-effectively and bundled as a stitch to fit the target of interest for animal or human use.

[0065] 2) Utilization of biocompatible materials: The Neuroweave includes at least four ultra-thin gold wires that are insulated with polyimide. The etched section along the length (1 -3 mm) of a wire contains (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) PEDOT:PSS as material interface to achieve desirable electrochemical properties. Applying009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00acrylate UV adhesive on each strand of the wire and twisting them allows mechanical fixation of the device. All the utilized materials are biocompatible and were evaluated for cytotoxicity.

[0066] 3) Low impedance for high SNR recording: A conductive layer of PEDOTPSS is electrodeposited on the contacts to achieve low impedances (e.g., 1 kHz impedance < 100 k ) for efficient signal recording of EEG signatures.

[0067] However, other electrode modifications to increase the surface area can be used. For example, the Au surface can be roughened electrochemically or by laser pulses to reduce the impedance and result in low impedance and therefore excellent recording quality.

[0068] 4) Better adhesion of the PEDOT:PSS by binding on the gold surface for semichronic and chronic use.

[0069] 5) Neuroweave wireless system for 4ch EEG monitoring: The compact wireless circuit supports 4-channel EEG sensing with a microprocessor, a multichannel differential amplifier, and a low-power Bluetooth module for real-time continuous data transmission to a client device such as a mobile platform or computer. A modular, rechargeable battery pack with a conductive magnetic connector ensures easy plug-in power and provides up to 10 hours of operation with a single 190mAh battery.

[0070] 6) Minimally invasive electrophysiological recording: A bundle of at least four wires with spatially controlled contacts distributed across the length of each p-electrode will be threaded on the target issue to enable comprehensive signal recording. The Neuroweave can reduce patient discomfort during post-operative monitoring on surgical sites and can be used as a semi -chronic or chronic diagnostic device for several clinical evaluations.

[0071] Additional aspects and implementations of example embodiments of the disclosed technology are described below.

[0072] Some disclosed embodiments provide a minimally invasive, suturable platform for brain monitoring.

[0073] Capturing infrequent or context-dependent brain events, such as epileptic seizures and sleep abnormalities, often requires continuous monitoring over several days. It is most practical and scalable when achieved with unobtrusive, high-fidelity wireless systems that patients can use at home. Current electroencephalography systems restrict patient mobility and require continuous electrode maintenance and sub-scalp solutions require surgical implantation that offer limited spatial coverage. In some embodiments of the NeuroWeave, gold-polyimide 009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00microthreads thinner than a human hair that can be stitched through the epidermis using standard suture tools and connected to a lightweight wireless recorder. In preclinical models, NeuroWeaves captured whisker-evoked potentials with accuracy comparable to skull screws and matched the performance of a commercial acquisition benchmark. Semi-chronic recordings in freely moving animals remained stable for several weeks, and 30-day histology showed minimal inflammation comparable to surgical sutures. Pilot human studies reproduced posteriordominant rhythms, photic responses, chewing artifacts, and sleep oscillations comparable to clinical electrodes. These results establish a minimally invasive, biocompatible neural interface that represents a new modality for high-fidelity brain monitoring beyond conventional laboratory and clinical constraints.

[0074] Continuous EEG is foundational to epilepsy diagnosis, sleep research, and neuroergonomics, yet no available electrode system achieves the combined requirements of long-term comfort, signal stability, and high fidelity in real-world settings. Clinical EEG remains reliant on gel-based surface electrodes that can require abrasive skin preparation, conductive paste, and frequent technician intervention. As the gels dry, the interface impedance increases and the signal quality deteriorates, which imposes a substantial maintenance burden for human subjects and clinical staff. Because seizure frequency varies widely across individuals, single-session recordings and patient self-report remain unreliable, and continuous multi-day monitoring is needed for precise characterization. Costs further exacerbate this gap. Hospitalization in an epilepsy monitoring unit (EMU) can exceed $40,000 per admission. This cost limits access in regions where -80% of the world’s 5 million new epilepsy cases occur each year.

[0075] A recently emerging class of “sub-scalp” technologies seeks to address these limitations by placing electrodes in the sub-galeal space, thereby bypassing the high-impedance epidermal barrier. These systems leverage macroscale contacts (-10 mm width) to achieve subkilohm (kQ) impedance and long-term stability. However, their clinical adoption remains constrained: The bulky form factors require centimeter-scale incisions, careful tunneling, and general anesthesia in an operating room, deterring many prospective patients. Reimbursement pathways remain unknown, and currently approved devices (e.g., Minder™ and UNEEG SubQ™) offer only unilateral or limited bilateral coverage, restricting spatial sampling. Reported complications — including scalp paresthesia, headaches, and sub-scalp hematoma — further underscore the limitations of current systems. Collectively, these issues highlight the need for a less invasive platform that supports high-fidelity, fully ambulatory brain monitoring.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0076] NeuroWeave, a minimally invasive recording modality (FIG. 16A), can be implemented to address these barriers through four integrated advances in clinical electrophysiology. FIG. 16A-16J shows various features, images, and benefits of some example embodiments of the NeuroWeave.

[0077] FIG. 16 A shows a schematic illustration of a wireless integrated NeuroWeaves system. Inset shows comparison of NeuroWeaves to current clinical modalities. FIG. 16B shows a photographic image of hair-thin NeuroWeaves device compared to clinical scalp electrodes. FIG. 16C shows simulation results of current density distribution across modalities (top) and electrical potential is highest for NeuroWeaves at 1.5 cm inter-electrode pitch (bottom). FIG. 16D shows photographic images of the fabrication process of gold-polyimide filaments. FIG. 16E shows electrochemical impedance before (n = 42) and after (n = 122) electrodeposition of PEDOT:PSS across 1 - 105frequency spectra (top). Histogram shows at least a magnitude difference between PEDOT:PSS and Au contacts at 1 kHz frequency (bottom, left). In vitro aging test of pristine PEDOT:PSS in 37°C saline show stability of impedance at 1 kHz frequency across 30 days study (bottom, right). FIG. 16F shows results of simulations which show bending up to small curvature of 8.9 mm results an elastic strain of 3%. FIG. 16G shows theoretical simulation of thread diameter and number of threads for choice of design. Star is the choice of design of NeuroWeaves for initial tests showing theoretical tension limit -2 N, which is close to experimental tensile tests of ~1.3 N. Dashed line resembles passing force of NeuroWeaves we performed to measure interfacial tension when passing through porcine skin. FIG. 16H shows a photographic image of the integrated wireless wearable system when attached to the NeuroWeaves device. FIG. 161 shows a photographic image of human subject demonstrating wearability of the cochlear inspired wireless module. Fig. 16J shows a diagram showing the data and power flow for the wireless module (top) and internal components of the printed-circuit board (PCB) when housed in a compact 3-D printed design with attached magnetic connectors for interchangeable batteries (bottom).

[0078] Some aspects of the NeuroWeave include: stitch-based electrodes that anchor within viable epidermis and can be implanted without anesthesia using a workflow identical to routine clinical suturing; a hair-thin (FIG. 16B), customizable thread architecture allows modulation of device length, contact spacing, and layout; adaptable implantation configurations can be selected to align with distinct clinical objectives. Finally, some embodiments of the NeuroWeave provide a compact wearable wireless system enables continuous EEG monitoring outside of traditional hospital infrastructure. These features provide stable recording 009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00performance while prioritizing comfort, ease of use, and operational feasibility for long-duration monitoring.

[0079] Some disclosed embodiments provide a wearable device for monitoring brain activity. For example, as shown in FIG. 161, some disclosed NeuroWeave devices and systems (e.g., 1000) are configured to be worn behind an ear. Other wearable configurations of NeuroWeave devices and systems are also possible.

[0080] The following paragraphs describe an example device architecture and wearable integration of NeuroWeaves in accordance with an example embodiment.

[0081] To implement this system, NeuroWeaves were engineered at the level of the device, materials, fabrication, and system integration. Spatial resolution and signal strength are jointly determined by electrode pitch in EEG systems. Based on simulations and human-use constraints, a 1.5-cm inter-electrode pitch was selected to maximize amplitude capture at the cutaneous surface (FIG. 16C). Each NeuroWeave included an insulated gold thread (~45 pm in diameter), which was selectively etched to expose a millimeter-scale recording site and then multiple of the threads were twisted together to form the final device structure (FIG. 16D). Wafer-scale batch processing is amenable to diverse device geometries for preclinical and clinical applications, as well as cost-efficient production. The fabrication scheme was refined by transitioning from multi-step photolithography to a streamlined hard-mask process using thermal release tapes, which reduced fabrication downtime and increased overall throughput.

[0082] Interfacial impedance is a key determinant of bioelectronic signal quality. Clinical guidelines from the American Clinical Neurophysiology Society (ACNS) recommend electrode impedances between 5 - 10 k for reliable EEG acquisition. Because each NeuroWeaves contact has an exceptionally small geometrical area, achieving low impedance requires a material with high volumetric capacitance and proven biocompatibility. Therefore, PEDOT:PSS was selected, which yields a porous interface rich in charge storage and capable of lowering impedance relative to bare gold (FIG. 16D). To control film thickness, a 100-s potentiostatic electrodeposition was used, which uniformly coated the etched sites and produced an order-of-magnitude reduction in impedance (FIG. 16E). However, PEDOT:PSS interfaces can delaminate during long-term exposure to biological environments. Thus, a surface-functionalization strategy was designed using 11 -mercapto- 1 -undecanol (MUD) followed by glycidyloxypropyltrimethoxysilane (GOPS) to promote covalent bonding between the conductive polymer and the gold surface. Contact-angle measurements confirmed the009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00hydrophilic end-group deposition, Fourier transform infrared spectra (FTIR) identified epoxide functionality, and Raman spectra revealed a narrowed full width at half maximum indicative of increased PEDOT chain ordering. Strikingly, 30-day aging studies performed at 37°C showed that both functionalized and pristine PEDOT:PSS coatings maintained sub-kilohm impedance with no measurable degradation, and the polyimide encapsulation exhibited no visible delamination at etched boundaries (FIG. 16E). These results allowed prioritization of pristine PEDOT:PSS for rapid manufacturing cycles.

[0083] Surgical sutures require high pliability and low memory to pass smoothly through tissue and maintain secure fixation. NeuroWeaves were thus engineered with mechanical properties that enable comparable handling during stitch-based implantation. The total device thickness (180-270 pm) yielded sufficient flexibility to achieve radii of curvature as small as 8.9 mm, which corresponds to the simulated yield point of the polyimide encapsulation layer (FIG. 16F). The thread-based construction allows NeuroWeaves to conform naturally to the scalp surface while matching the profile of standard scalp sutures (FIG. 16G). Tensile testing of bundled threads showed that five gold filaments produced a strength of ~1.3 N, sufficient to withstand insertion forces. Applying medical adhesive further helped prevent breakage at the needle-thread junction. Sutured NeuroWeaves on porcine skin generated interfacial tensions below 40 mN, similar to surgical sutures (FIG. 16G). This suggests minimal tissue disruption or discomfort during placement for clinical deployment.

[0084] To support continuous ambulatory recording, a wearable wireless unit inspired by the form factor of the external processors for cochlear implants was developed (FIG. 16H). The device weighed 18.25 g when positioned behind the ear, reducing mechanical load and supporting day-to-day wear (FIG. 16H AND FIG. 161). Swappable magnetic connectors allowed the batteries to support eight-hour recording sessions and be exchanged without interrupting data collection (FIG. 16J). Recorded signals are streamed in real-time to a handheld tablet or computer interface for monitoring and analysis, and the NeuroWeaves can also connect to clinical touch-proof leads during supervised evaluations.

[0085] Prior to preclinical validation, thee biocompatibility of all device materials was assessed. In vitro cytotoxicity and biocompatibility assays confirmed no adverse cellular responses, and all materials met ISO 10993-5 cytotoxicity requirements. Next, the robustness of PEDOT:PSS contacts was evaluated using a customized roughened probe, and impedances in saline remained sub-kQ after 10 abrasive cycles. To simulate placement within the epidermis,009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00this experiment was repeated in vivo and observed stable contact impedances after 30 positioning cycles, which is more than sufficient for clinical handling.

[0086] To test broadband activity and signal fidelity, a 12-cm NeuroWeaves device was sutured with a 1-mm contact into the epidermis near the right primary sensory cortex of an anesthetized rat. Epidural screws were implanted on the frontal bone to serve as control electrodes. Both systems were connected to a commercial acquisition unit (Intan Technologies LLC) to validate recording performance in the same animal (n = 3) (FIG. 17A). NeuroWeaves exhibited in vivo impedances in the expected range (mean 3.5 kQ, n = 2 contacts) (FIG. 17B). This is consistent with the ~570-fold smaller geometric surface area of a single NeuroWeave contact compared to an epidural screw (-0.03 mm2versus -17 mm2). Baseline recordings from both electrodes showed similar waveform fluctuations in raw and band-pass filtered (1 - 100 Hz) traces, with slightly larger amplitudes observed in epidural screws due to their closer proximity to cortical tissue (FIG. 17C).

[0087] Whisker deflection in rats produces robust, time -locked somatosensory evoked potentials (SSEPs), providing a reliable model for assessing temporal fidelity of neural recordings. It was hypothesized that NeuroWeaves could capture these SSEPs transcutaneously because the skull-to-cortex separation is small in rats. Air-puff stimuli were therefore delivered to all contralateral whiskers to generate a large, evoked response. Both electrode systems recorded clear SSEPs characterized by an initial positive deflection, a subsequent negative component, and a prominent late positive wave consistent with known late somatosensory activity (FIG. 17D). Notably, NeuroWeaves exhibited a mean latency of -11 ms compared to -15 ms for epidural screws, potentially reflecting differences in electrode location relative to the barrel cortex.

[0088] These location-dependent differences motivated testing of whether NeuroWeaves could resolve spatial variation in whisker-evoked responses. The number of NeuroWeaves contacts were increased to four recordings channels to assess latency differences for spatial localization. The contacts were sutured in a loop spanning contralateral and ipsilateral positions. During contralateral stimulation near the whisker-barrel cortex, randomized trials showed a significant latency difference between contralateral and ipsilateral contacts (mean -11 ms versus -16 ms, p = 0.0026), whereas ipsilateral-only stimulation produced no significant difference (p = 0.0978). Also, reproducibility across animals was confirmed by additional in vivo impedance, baseline, and whisker-evoked measurements.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0089] After validating signal fidelity with the tethered system, performance was evaluated using a custom wireless platform (FIG. 17E). The wireless unit samples at 1,000 Hz and exhibits a -3 dB bandwidth at 342 Hz. Its signal-to-noise ratio (SNR) is -15 dB at 1 pV peak-to-peak simulated waveform. This is sufficient to resolve the temporal dynamics of whisker-evoked responses. To benchmark wireless performance against the commercial system, two NeuroWeaves devices were implanted in the same animal (n = 3) with three contacts each in parallel near the right somatosensory cortex — one connected to the Intan system and the other to the wireless unit. A handheld tablet placed inside the Faraday cage received the transmitted data, and benchtop testing demonstrated a mean packet-loss rate of -0.06% over a 2-hour recording within a 10-cm transmission distance. Filtered baseline activity acquired through the wireless system showed broadband neural dynamics across all channels under anesthesia (FIG.17F). During puff stimulation, the wireless system captured clear, time-locked somatosensory-evoked potentials that closely matched recordings from the commercial system when compared across sliding 5-second trial-averaged windows (FIG. 17G). Moreover, both systems produced comparable 1 -second trial-averaged scalograms with similar temporal and spectral structure and peak power concentrated in the low-frequency band (-5 - 20 Hz) (FIG. 17H). These comparative experiments were repeated across multiple animals and observed consistent agreement in signal amplitude, response latency, and spectral profiles between the two systems.

[0090] Robust detection of pathological neural activity is essential for translational utility, so NeuroWeaves were evaluated during chemically induced seizures. The GABAA receptor antagonist bicuculline was used to elicit focal cortical discharges. A small scalp flap was elevated near the frontal bone, and a cranial opening was made to expose the dura. This allowed suturing of the NeuroWeaves in close proximity to the induction site. Bicuculline was dissolved in dimethyl sulfoxide (DMSO) to enhance membrane permeability and applied topically to the dura while recordings were acquired with the wireless system (FIG. 171). Seizure onset occurred 23 minutes later, consistent with slow diffusion across the dura (FIG. 17J). The resulting activity consisted of burst-pause discharges with strong energy in the 8-15 Hz and 20-80 Hz bands that persisted for -160 seconds. These electrographic bursts were accompanied by whisker twitching temporally aligned with the activity, which is suggestive of early facial motor involvement and may represent an early clonic correlate (FIGS. 17J-17K).

[0091] To assess deeper limbic activity, bicuculline was injected into the amygdala while recording with the Intan system. Band-pass (1 - 300 Hz) traces revealed spike discharges in two channels -12 seconds after induction, corresponding to contacts nearest the injection site. A -7 009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00Hz rhythm emerged ~40 seconds later with accompanying surface spikes, indicating cortical recruitment during propagation of the limbic seizure. These results show that NeuroWeaves capture seizure onset and propagation across brain regions essential for translational monitoring.

[0092] FIG. 17 A shows a schematic illustration of the electrode validation tests of NeuroWeaves compared to control epidural screws when connected to a commercial acquisition system in the same animal (n = 3). FIG. 17B shows in vivo impedances comparison between NeuroWeaves and epidural screws at 1 kHz frequency. FIG. 17C shows raw and filtered (1 -100 Hz) baseline activity under anesthesia. FIG. 17D shows trial averaged responses (black lines) and single trials (grey) for all channels of NeuroWeaves and epidural screws at 1 Hz puff stimulation (n = 207 trials) and 2 Hz puff stimulation (n = 447 trials). FIG. 17E shows a schematic illustration of the wireless validation tests of NeuroWeaves tethered to custom wireless board and NeuroWeaves connected to commercial acquisition system (n = 3). FIG. 17F shows filtered (1 - 100 Hz) baseline of the three channels after transferring data to a handheld device under anesthesia. FIG. 17G shows a comparison of the trial averaged whisker evoked potentials between wireless and commercial tethered module over a 5-second sliding window. FIG. 17H shows scalograms comparison of the wireless (top) and commercial (bottom) of a 1-second trial averaged response showing power concentration in the low frequency bands (-5 -20 Hz). The commercial system has a minimal broader frequency power concentration up to 100 Hz, which is confirmed with baseline measurements and could be a heart-rate artifact. FIG. 171 shows a photographic image of the chemically induced seizure topically under anesthesia with NeuroWeaves device stitched near flap site and connected to the wireless board. FIG. 17J shows filtered (1 - 100 Hz) demonstrating evolution from baseline to seizure event for all channels. FIG. 17K shows a zoomed-in window of the electrographic seizure from red dashed box in (FIG.l 7J). Bottom trace shows a zoomed-in time window to demonstrate the rhythmic burst events from the top dashed line trace.. FIG. 17L shows a scalogram of a 2-second window shows peak power concentration of the seizure event in the -8-15 Hz and 20-80 Hz bands.

[0093] Having established acute recording performance, NeuroWeaves were evaluated in semi-chronic preparations to assess stability over extended timescales in freely moving rats (FIGS. 18A-18C). For these studies, the contact length was increased to 3 mm and the overall device length to 18 cm for stability and flexibility. To demonstrate material versatility, NeuroWeaves were fabricated using either FDA-cleared platinum nanorods (PtNR) or PEDOT:PSS coatings (FIG. 18D). Devices were tunneled transcutaneously from the thoracic region for reference and ground channels, and the recording contacts were positioned over the 009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00cortex. Semi -chronic impedance measurements across materials and animals showed recording durations of ~2 weeks (n = 3), with early termination primarily due to device displacement caused by animal activity rather than material degradation.

[0094] To confirm electrode functionality over time, whisker-puff validation was performed under anesthesia for a mean of 10 days in PEDOT:PSS and Pt NR NeuroWeaves (n = 2). Several recordings exhibited a polarity inversion of the evoked response, likely reflecting minor contact relocation (relative to the reference) associated with tissue healing or movement; sham controls confirmed the physiological origin of the responses (FIG. 18F). Then, recordings were performed in untethered rats and different behavioral activities (n = 2) were measured. For instance, ~21 minutes of natural sleep was recorded and 16 spindles were detected during this interval in PtNR NeuroWeaves (FIG. 18G). Notably, some spindles were preceded by slow-wave activity across multiple channels, others showed a preceding slow wave on only one channel, and some occurred without any preceding slow-wave activity (FIG. 18H). This variability is consistent with prior reports that spindle-slow-wave coupling is heterogeneous and that many — but not all — spindles are expressed in association with local slow waves or K-complex-like events. These spindles exhibited strong 10 - 14 Hz activity, in agreement with characteristic rat spindle frequencies (10 - 16 Hz). To further illustrate freely moving behavior, NeuroWeaves recordings captured distinct activity patterns during emergence from anesthesia, spontaneous movements, and chewing artifacts (FIGS. 18J-18M). Finally, histological analysis of CD3, CDllb, a-SMA, and FOXP3 showed minimal T-cell infiltration, limited myeloid recruitment, low fibrotic response, and stable regulatory T-cell activity over 30 days (FIG. 18N).

[0095] FIG. 18A shows a schematic illustration of integrated wireless NeuroWeaves system in a freely-moving rat. FIG. 18B shows a photographic image of the embedded wireless module in the pocket of the rat jacket. Red dashed line shows the connectorization of the breakout board from the NeuroWeaves connection-end to the wireless board via flexible cable connector. FIG. 18C shows a photographic image showing the ground and reference electrodes with three 3 -mm electrode widths design for ambulatory wireless demonstration. FIG. 18D shows a scanning electron microscopy of the PEDOT:PSS contact (top) and FDA-cleared PtNR (bottom). FIG. 18E shows in vivo impedances across three rats over extended periods of recordings and red-dashed line shows early termination of the PtNR due to NeuroWeaves relocation from excessive dynamic movement of the rat after 1 -week post implantation. FIG.18F shows trial averaged responses (black lines) and single trials (grey) for all materials over extended recording sessions when tethered to the commercial system for validation prior to 009062.8590. WO00M86161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00connectorization of the wireless module for freely moving behavior recording sessions (n = 2). FIG. 18G shows multitaper spectrogram filtered showing an example of a sleep session with strong power concentrated in the low frequency bands for PtNR NeuroWeaves. Dashed lines show sleep and awake events. FIG. 18H shows spindles and slow-wave associated spindles across all recording channels when recording wirelessly. FIG. 181 shows inset of the multitaper spectrogram of Spindle 10 for channel 1 shows strong 10 - 14 Hz power concentration demonstrating spindle activity. FIG. 18J shows a scalogram showing transition from anesthetized to awake state for channel 1 with trace overlay. FIG. 18K shows a scalogram showing chewing events for channel 1 with trace overlay. FIG. 18L shows filtered (1 - 100 Hz) traces of all wirelessly recording channels for transition state from anesthesia to awake. FIG.18M shows filtered (1 - 100 Hz) traces of all recording channels for chewing event. FIG. 18N shows biomarker studies for chronic periods between Nylon 4 - 0 surgical sutures and PEDOT:PSS NeuroWeaves showing minimal to no adverse events (n = 6).

[0096] Translational feasibility requires adherence to clinical sterilization standards, and fully assembled NeuroWeaves — mounted on clinical connectors — were compatible with conventional sterilization procedures. A pilot clinical evaluation (n = 2) was conducted in a healthy participant. For these studies, devices were 18 cm in length with 3-mm contact windows, and surgical skin markers were used to guide suturing. As an initial demonstration, PEDOT:PSS NeuroWeaves were positioned over the occipital scalp and recorded a robust posterior dominant rhythm (PDR) that emerged after eye closure. In subsequent experiments, the NeuroWeaves were maintained near the occipital region and added two standard clinical electrodes at 02 and FP2 locations according to the international 10-20 system (FIG. 19 A). Interfacial impedances were comparable across electrodes, with NeuroWeaves exhibiting slightly lower values than the clinical control (9.5 versus 10 kQ) (FIG. 19B). Baseline EEG activity (1 - 100 Hz) showed NeuroWeaves with a narrower distribution of amplitudes, consistent with reduced baseline variability; Levene’s test confirmed unequal variances (p = 0.022). Posterior dominant rhythm was reproducible across sessions, with electrodes near the occipital lobe capturing clear alphaband activity (8 - 12 Hz) (FIG. 19C). These changes were corroborated by a mean power shift across electrodes between eyes-open and eyes-closed states (FIG. 19D) and by a statistically significant increase in alpha power for NeuroWeaves between open and closed conditions (p = 0.0002) (FIG. 19E).

[0097] Photic stimulation is routinely used to probe visual cortex responsiveness and to screen for photosensitivity. In healthy individuals, EEG activity typically results in photic 009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00driving effect which represents repetitive visual evoked potentials. It was hypothesized that NeuroWeaves and the clinical 02 electrode, owing to their proximity to the visual cortex, would capture stimulus -locked responses to photic stimulation. Power spectral densities revealed clear peaks at the stimulation frequencies with substantial overlap between NeuroWeaves and 02 (FIG. 19F). Signal-to-noise ratios were comparable, with slightly lower power for NeuroWeaves, likely reflecting small differences in electrode position relative to the underlying cortex (FIG. 19G). To assess sensitivity to movement-related artifacts, chewing was induced and the largest muscle activity was observed in the clinical FP2 channel, which lies closest to the temporalis muscles (FIG. 19H).

[0098] Finally, to assess comfort and signal fidelity in a clinically relevant context, a short sleep study was conducted. During relaxed wakefulness, NeuroWeaves recorded clear alpha oscillations (FIGS. 19I-19K). As the subject transitioned into non-rapid eye movement (NREM) sleep, delta power gradually increased, and spindle events of at least 500 ms duration with waxing-waning morphology were detected and spectral content within the conventional spindle band (11 -16 Hz) was detected (FIGS. 19L-19N). Post-explant inspection showed minimal to no visible damage to the recording contacts, supporting the mechanical robustness of the device during clinical handling.

[0099] FIG. 19A shows a photographic image showing NeuroWeaves implanted near the occipital region with clinical electrodes acting as control (left) (n = 2 trials). Approximate location of the NeuroWeaves according to the 10-20 International system (right). FIG. 19B shows in vivo impedance comparison between NeuroWeaves channel versus clinical 02 electrode. FIG. 19C shows filtered traces (1 - 100 Hz) reveal transition state between eyes open and eyes closed for all channels showing strong PDR response for NeuroWeaves and 02 channels. FIG. 19D shows alpha power of all channels shows a strong convergence in the y = x line segment with a mean shift of power from eyes closed to eyes open. FIG. 19E shows windowed alpha power was greater during eyes-closed than eyes-open, confirmed by a permutation test (p = 0.0002). FIG. 19F shows power spectral densities across 10 - 30 Hz flash frequencies show clear peaks of the NeuroWeaves and scalp 02 electrode demonstrating driving photic response in a healthy subject. FIG. 19G shows comparable SNR between NeuroWeaves and 02 clinical electrode across flash frequencies. FIG. 19H shows filtered (1 - 100 Hz) traces of all channels during chewing event showing strong spikes for the FP2 clinical channel due to close proximity of the temporalis muscle. FIG. 191 shows restful awake event shows strong PDR for the filtered traces for the NeuroWeaves and 02 electrode. FIG. 19J shows alpha power 009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00distribution confirming strong PDR for the channels near the occipital scalp region. FIG. 19J shows multitaper spectrogram show power concentration in the ~8 - 12 Hz during awake closed eyes. FIG. 19L shows detected spindle event during NREM showing waxing -waning morphology across recording channels. FIG. 19M shows an example of a filtered trace (11 - 16 Hz) trace showing detected spindle when applying algorithm. FIG. 19N shows inset of the multitaper spectrogram show power concentration in the 11- 16 Hz for the spindle event.

[0100] The results presented here demonstrate that suturable thread-based neural interfaces can extend electrophysiological monitoring into a regime that has traditionally required rigid electrodes or surgical implantation. NeuroWeaves integrate materials engineering, device architecture, and clinical workflow considerations to overcome long-standing issues of comfort, invasiveness, and spatial constraint. By combining hair-thin gold-polyimide filaments with low-impedance conductive coatings and a lightweight wireless platform, the system achieves stable recordings across acute, semi-chronic, and human pilot studies. These capabilities demonstrate that epidermal suturing — long used in routine medical practice — can serve as a viable route for transcutaneous neural access without the burden of gels, adhesives, or surgical exposure.

[0101] The ability to resolve whisker-evoked responses, seizure dynamics, sleep rhythms, and photic entrainment using the same stitched interface suggests that the spatial reach of volume conduction may be more permissive. Differences in latency across sutured positions also hint at the potential for simple stitch patterns to extract spatial information, even without penetrating or intracranial placement. Moreover, the semi-chronic results indicate that thread-based contacts can remain stable in freely moving animals despite tissue motion, healing, and behavioral perturbations, an encouraging sign for long-term human use.

[0102] Human pilot data further revealed that NeuroWeaves can reproduce typical physiological signatures — including posterior dominant rhythm, sleep transitions, and photic responses — at a level comparable to clinical electrodes. This raises the possibility that suturable interfaces could complement or, in selected contexts, substitute for conventional surface EEG systems. The simplicity of implantation also suggests potential for decentralized or home -based monitoring, particularly in settings where access to prolonged EEG remains limited.

[0103] Critically, the suturable mechanical fixation and direct epidermal interface of NeuroWeaves provide inherent stability analogous to surgical sutures, supporting continuous009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00recordings over days to weeks without gel degradation or adhesive failure, and positioning this platform for truly extended ambulatory use.

[0104] Examples of materials, methods, and techniques based on the disclosed embodiments are described below.

[0105] In an example fabrication of NeuroWeaves, the following steps were performed. Materials and Methods

[0106] (1) Photolithography steps

[0107] NeuroWeaves were fabricated using a trench-assisted wire transfer process adapted for long, insulated gold microwires (California Fine Wire Co.). SU-8 2005 (Kayaku Advanced Materials Inc) was spin-coated onto a silicon wafer and patterned by photolithography to form ~65 pm- wide trenches that guided wire placement. Gold wires (8 cm length) were cut from a spool, straightened using isopropyl alcohol and gentle rolling, and manually positioned into the SU-8 trenches.

[0108] A separate glass wafer was coated with a thick layer of positive photoresist (AZ 12XT-20PL-10, MicroChemicals; 12-14 pm) and partially cured to form an adhesive surface. This semi-cured film was then brought into contact with the silicon wafer, enabling transfer of the gold wires from the SU-8 trenches onto the glass substrate during heating. Following transfer, the wafer was fully cured on a hot plate at 110°C to stabilize the embedded wires. A second layer of positive photoresist was subsequently spin-coated and cured to encapsulate the wires and remove residual solvent.

[0109] Photolithography using a Karl Suss MA6 mask aligner and mylar photomasks (FineLine Imaging) defined openings along the wire length corresponding to electrical contacts and interconnects. A brief flood exposure was applied prior to etching to suppress foaming of the positive thick photoresist. Selective removal of the polyimide insulation was then performed using a mixed oxygen and tetrafluoromethane plasma for 30 - 40 minutes in 5-minute intervals by inductively coupled plasma reactive ion etching (ICP-RIE) at 100W-10W power ratio while maintaining temperature control at 20°C (Trion Minilock Phantom III ICP, Trion Technology). This cooling setup within 5-minute intervals minimized microcracking of the thick photoresist, and produced exposed regions for electrical interfacing and recording channels.009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0110] (2) Hard-mask process

[0111] A thermal-release-tape (TRT)-assisted process was used to microfabricate long insulated gold threads with patterned exposed regions. Thermal release tape (Semiconductor Equipment Corp.) was laser-cut using a CO2 laser to define the wire placement layout and laminated onto 6-in or 8-in silicon wafers. Gold wires were cut to the required lengths, straightened using isopropyl alcohol and gentle rolling, and placed onto the predefined TRT regions. Both wafer formats were used: the 6-in TRT layout incorporated serpentine designs accommodating thread lengths up to ~12 cm and provided four TRT lanes per wafer, each carrying two wires; the 8-in format used straight-line patterns supporting 16-18 cm threads and offered up to ten TRT lanes per wafer, each holding four wires, enabling significantly higher throughput.

[0112] A custom aluminum shadow mask (~1 mm thick) was then aligned on top of the wafer to expose the intended contact and interconnect sites. Selective removal of the polyimide insulation was performed by dry etching in a mixed oxygen and tetrafluoromethane plasma for 30 - 40 minutes at 200 W RIE (Oxford Plasmalab 80+, Oxford Instruments). After etching, the wafer was placed on a 120°C hot plate for at least two minutes to release the wires from the TRT. Retrieved wires were prepared for electrochemical testing by attaching copper leads with silver conductive paint (PELCO Conductive Silver Paint, Ted Pella Inc.) at the connection sites for impedance spectroscopy in phosphate-buffered saline (silver-silver chloride (Ag / AgCl) reference, platinum (Pt) counter electrode).Inlegration and Conneclorizalion

[0113] After deposition of the conductive material, individual threads were mounted onto a custom mechanical assembly tool and twisted to form the NeuroWeaves bundle. The distal tip of the NeuroWeave, positioned at least 1 cm from the first electrode contact, was then threaded through a medical needle (Richard- Allan®) to create the attachment knot. To midgate mechanical stress at the needle-NeuroWeaves interface, a biocompatible medical adhesive (215-CTH-LV-UR-SC / 10SYMR, Dymax®) was applied to the knot region.

[0114] For connectorization, at least 0.5 cm of insulation was removed from the end of each NeuroWeaves bundle to allow attachment to an interconnector or breakout interface for tethered recordings with the wireless or Intan systems. These exposed endpoints were soldered using low-temperature solder paste (SMDLTLFP10T5, CHIPQUICK). When touch-proof009062.8590. WO00X186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00clinical leads were used, the exposed NeuroWeaves wires were soldered directly to the lead terminals, and a rigid support structure was added to minimize mechanical load on the threads. Porcine Skin Incision Experiments

[0115] Porcine test material was purchased from Stellen Medical, LLC (Cat. No. 1-188) to perform the incision experiments. A mechanical testing apparatus (Mark-10) was used to evaluate knot strength and interfacial tension (passing force) for NeuroWeaves and Nylon 4-0 sutures (ETHILON®) on ~1 mm thick porcine skin. For knot strength measurements, the needle was inserted halfway through the skin to allow the probe to grasp the needle body, and the knot strength was defined as the tension required for the knot to pass through the tissue. These tests were performed using a 100 N force gauge.

[0116] For interfacial tension experiments, the needle was fully passed through the skin so that only the tension transmitted through the suture was. A slight increase in interfacial tension was observed, likely due to gradual drying of the porcine tissue. These measurements were acquired using a 0.5 N force gauge.Surgical Procedures of Preclinical Cases

[0117] All animal experiments were approved by the University of California San Diego (UCSD) Institutional Animal Care and Use Committee under protocol SI 6020. Animals were initially induced with isoflurane anesthesia (4 - 5%), and all surgical procedures were conducted under maintained isoflurane (2 - 3%) delivered through a precision vaporizer and scavenged with charcoal filters. Anesthetic depth was continuously monitored by tracking heart rate (MouseSTAT® Jr.), respiratory rate, and responsiveness to toe pinch, while body temperature was maintained using a heated waterbed. Before recording, each animal was transitioned from isoflurane to a ketamine / xylazine cocktail (80 / 20), and data collection commenced only after full withdrawal from isoflurane. Subdermal needle electrodes were used for ground and reference and were placed along the scalp midline, with minor adjustments made to minimize ECG artifacts.

[0118] (1) Acute recording cases

[0119] For acute experiments, NeuroWeaves were sutured subdermally on the scalp above the right hemisphere, centered approximately over the somatosensory cortex, such that the number of skin insertions matched the number of device contacts. In some experiments, stainless-steel screws (1 / 8” EEG Screw, Pinnacle Technology De, LLC) were implanted 009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00alongside the NeuroWeaves to enable recording comparisons. These screws were positioned along the anterior-posterior axis of the frontal and parietal bones on the right hemisphere with an approximate pitch of 0.5 cm. To evoke sensory activity, air-puff whisker stimulation (PV830 Pneumatic PicoPump, WPI) was delivered through a microcapillary tube to move the whiskers on the contralateral side at 40 psi.

[0120] All NeuroWeaves used in these studies had a contact width of 10 pm, an interelectrode pitch of 1 cm, and a total device length of 12 cm. For electrode comparison tests (n = 3), recordings were acquired using a commercial system (Intan Technologies LLC). For wireless benchmarking (n = 3), NeuroWeaves were recorded using both the commercial tethered system and our custom wireless platform for direct comparison. Table 4 summarizes all experiments performed in the acute cohort.

[0121] (2) Induction of seizures

[0122] To induce seizures, a 3 x 3 mm craniotomy was created over the somatosensory cortex using a surgical drill. Bicuculline (5 mM in 10 pL DMSO) was administered either by topical application onto the exposed cortex or by direct injection into the amygdala (-2.8 mm anteroposterior, 5 mm mediolateral, 8.8 mm dorsoventral) using a 1 pL Hamilton syringe mounted on a stereotaxic holder. Table 4 summarizes all experiments performed for seizures.

[0123] (3) Semi-chronic cases

[0124] For chronic experiments, a fully implanted approach was used to prevent animals from scratching or dislodging the NeuroWeaves. A 1 cm scalp incision was made, followed by gentle tissue scraping to expose a clean, dry bone surface. A secondary incision was created on the dorsal thoracic region approximately 5 cm caudal to the head. The NeuroWeaves were then tunneled subcutaneously from the back incision to the head using fine surgical forceps. The distal tip of the NeuroWeave was secured to the skull using a UV-curable polymer (Tetric Evoflow Syringe Trans, 2 g). The device breakout connector was permanently housed within the animal jacket (Lomir Biomedical Inc.). Prior to wireless recording sessions, NeuroWeaves were connected to the commercial acquisition system to measure electrochemical impedances. During recordings, a wireless system with a battery was attached to the breakout connector and placed securely inside the jacket pocket and subsequently removed after each session. On separate days, whisker-barrel stimulation was performed to evaluate recording performance across the week. Table 4 summarizes all experiments performed in the chronic cohort.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00Clinical Procedure

[0125] An epilepsy monitoring unit technologist assisted in the preparation and adhesion of the scalp EEG. Prior to the recording, the human subject’s scalp was prepared at the intended scalp EEG adhesion and NeuroWeave suture sites using alcohol wipes and an abrasive gel, per the institution’s clinical standards, to minimize impedance and artifacts. The FP2 and 02 scalp EEG channels were placed using the international 10-20 system for EEG placement, which correspond to approximately the right frontal and right occipital regions, respectively. These regions were chosen to gather physiologic signals, such as a posterior dominant rhythm (from the 02 channel) and eye blinking artifacts (from the FP2 channel). An electrode was placed on the chest to serve a reference. Following sterilization, the NeuroWeaves electrode was sutured in place, using a needle driver, next to the 02 electrode by a physician to primarily detect the posterior dominant rhythm.

[0126] A 1-hour recording, similar in duration to the usual routine EEG recordings performed at our institution, was performed and captured several states, including awake, drowsiness, and stage II sleep. An impedance check was conducted on the NeuroWeaves, and approximately 9.5kOhm was noted a few minutes after application, which was comparable to the EEG leads. During the awake state, normal physiologic data was captured, and the subject was asked to perform similar tasks to those that occur during a typical clinical routine EEG recording, including: opening and closing their eyes (to capture blinking and posterior dominant rhythm appearance), moving their head, and chewing. Additionally, photic stimulation was performed at increasing frequencies up to 30 Hz to capture photic driving, a typical physiologic response. Finally, the patient was allowed to rest for 20 minutes, and characteristic features of drowsiness and stage II sleep were seen.

[0127] After the recording was completed, the NeuroWeaves electrode and EEG electrodes were removed and the sites were cleaned with minimal bleeding noted. There was minimal discomfort during the NeuroWeaves suturing and none during removal, and there was no pain noted later that day or a week later; on a 1 -week post-procedure check-in by a physician, there was no inflammation or infection noted at the site. All procedures and consent were conducted under the auspices of the local Institutional Review Board.

[0128] The disclosed embodiments support inter alia the following technical solutions.

[0129] 1. A device for monitoring brain activity, comprising: a plurality of wires including a plurality of electrodes configured to obtain electroencephalogram (EEG) signals 009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00associated with different regions of a scalp, the plurality of electrodes configured to be threaded into a skin layer beneath a surface of the scalp using the plurality of wires to enable positioning of the plurality of electrodes within the skin layer at the different regions, wherein each wire comprises: an electrically conductive inner portion, an insulating layer formed around the electrically conductive inner portion, one or more sections along a length of the wire at which the insulating layer is not present exposing part of the electrically conductive inner portion, wherein two or more sections are spaced apart from one another along the length of the wire according to a predetermined spacing, and an electrode at each of the one or more sections to allow measurement of the EEG signals using the electrically conductive inner portion, wherein the plurality of wires are bundled together such that a first end of each wire is couplable to a tool to enable placement of the plurality of electrodes within the skin layer, and wherein the electrically conductive inner portion is exposed at a second end of each wire to enable acquisition of the EEG signals.

[0130] 2. The device of solution 1 , wherein the skin layer corresponds to an epidermis layer of the scalp.

[0131] 3. The device of solution 1, wherein the skin layer is beneath a dermis layer of the scalp, wherein the plurality of electrodes is configured to be positioned at the different regions within the skin layer via injection using the plurality of wires.

[0132] 4. The device of solution 1, wherein the plurality of wires includes at least four wires.

[0133] 5. The device of solution 1, wherein some or all of the plurality of electrodes include a biocompatible conductive polymer electrodeposited on a surface of the electrode and configured to interface with the scalp.

[0134] 6. The device of solution 5, wherein some or all of the plurality of electrodes include a surface modification or a coating.

[0135] 7. The device of solution 1, wherein the insulating layer comprises a biocompatible material.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0136] 8. The device of solution 1, wherein the electrode is customizable in width along the length of the wire based on the one or more portions of the electrically conductive inner portion that are exposed.

[0137] 9. The device of solution 1, wherein the second end of each wire is configured to couple to a potentiostat, a connector, or a circuit board.

[0138] 10. The device of solution 1, wherein the plurality of wires that are bundled together form a twisted configuration, and wherein the plurality of electrodes are spaced apart from one another over a length of the twisted configuration according to the predetermined spacing.

[0139] 11. The device of solution 1, wherein the electrically conductive inner portion has a diameter of at least 40 microns, wherein the insulating layer has a thickness between 5 to 10 microns, and wherein the one or more sections are between 1 to 3 mm wide along the length of the wire.

[0140] 12. The device of solution 1, wherein the tool corresponds to a medical needle or an injection tool.

[0141] 13. A wearable system for monitoring brain activity, comprising: a device according to any one of solutions 1-12; a battery configured to supply power to the device; and a wireless circuit comprising: a flexible connector configured to interface with the plurality of electrodes of the device to receive the EEG signals, at least one connector configured to couple the wireless circuit to the battery, at least one processor configured to enable wireless transmission of the EEG signals to an external device, and a multichannel differential amplifier communicatively coupled to the at least one processor and the plurality of electrodes of the device.

[0142] 14. The wearable system of solution 13, wherein a first end of the flexible connector is coupled to the second end of each wire of the device and a second end of the flexible connector is configured to couple to an input of the wireless circuit.

[0143] 15. The wearable system of solution 13, comprising a first housing and a second housing configured to couple to the first housing to allow the system to be worn behind009062.8590. WO00M86161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00an ear, wherein the battery is disposed within the first housing and the wireless circuit is disposed within the second housing.

[0144] 16. The wearable system of solution 13, wherein the at least one processor comprises an antenna.

[0145] 17. A method of monitoring brain activity, comprising: using a plurality of wires comprising a plurality of electrodes to position the plurality of electrodes into a skin layer beneath a surface of a scalp such that the plurality of electrodes are positioned within the skin layer at different regions of the scalp, wherein: each of the wires comprises an electrically conductive inner portion and an insulating layer formed around the electrically conductive inner portion, each electrode is associated with one of the wires and is disposed at a section along a length of the wire at which the insulating layer is not present to allow measurement of brain activity using the electrically conductive inner portion, and each of the different regions is associated with one or more of the electrodes: obtaining electroencephalogram (EEG) signals associated with the different regions of the scalp using at least some of the plurality of electrodes, and providing the EEG signals as output to enable monitoring of brain activity based on the EEG signals.

[0146] 18. The method of solution 17, wherein using the plurality of wires comprises injecting or suturing the plurality of electrodes into the skin layer, wherein the skin layer corresponds to an epidermis layer or a dermis layer of the scalp.

[0147] 19. The method of solution 17, wherein using the plurality of wires comprises: before positioning the plurality of electrodes into the skin layer, twisting the plurality of wires together to form a bundled configuration of the plurality of wires such that the plurality of electrodes are spaced apart from one another over a length of the bundled configuration according to a predetermined spacing, and positioning the plurality of electrodes into the skin later while at least some of the plurality of wires are in the bundled configuration

[0148] 20. The method of solution 17, wherein the plurality of wires includes at least four wires.

[0149] 21. The method of solution 17, wherein using the plurality of wires comprises coupling a first end of each wire to a device to enable positioning of the plurality of electrodes within the skin layer at the different regions of the scalp.009062.8590. WO00M86161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0150] 22. The method of solution 17, wherein some or all of the plurality of electrodes include a biocompatible conductive polymer disposed on a surface of the electrode and configured to interface with the scalp.

[0151] 23. The method of solution 17, wherein providing the EEG signals as output comprises receiving the EEG signals via a connector coupled to a second end of each wire at which a portion of the electrically conductive inner portion is exposed.

[0152] 24. A micro-electrode stitch device comprising: a plurality of ultra-thin wires bundled into a single weave wherein the ultra-thin wires are comprised of insulated wires that have sections along the length that are etched for recording and data acquisition.

[0153] 25. The micro-electrode stitch device of solution 24, wherein the plurality of ultra-thin wires includes at least four wires.

[0154] 26. The micro-electrode stitch device of solution 24, wherein the insulated wires include a gold wire.

[0155] 27. The micro-electrode stitch device solution 26, wherein each insulated gold wire has as a diameter of at least 40 pm and is coated with a polymer insulation that is made of poly imide.

[0156] 28. The micro-electrode stitch device of solution 26, wherein the polyimide is a common biocompatible and flexible material that is used for neural probes.

[0157] 29. The micro-electrode stitch device of solution 27, wherein total thickness of the polyimide insulation is between about 5 pm and 10 pm.

[0158] 30. The micro-electrode stitch device of solution 24, wherein the ultra-thin wires are twisted together with spatial controlled contacts.

[0159] 31. The micro-electrode stitch device of solution 27, wherein the contacts are etched using microfabrication techniques and electrodeposited with PEDOT:PSS.

[0160] 32. A system of monitoring brain activity comprising: ultra-thin thread-based electrodes that are bundled and configured to be stitched into the epidermis of skin or injected beneath the dermis of skin; and a data processing unit for real-time continuous data transmission to a client device such as a mobile platform or computer.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00

[0161] 33. The system of monitoring brain activity of solution 32, wherein the data processing unit comprises a microprocessor, a multichannel differential amplifier, and a low-power Bluetooth module.

[0162] 34. A system, device, or method of recording electroencephalogram (EEG) data using engineered electrodes substantially as shown and described.

[0163] The above detailed descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology as those skilled in the relevant art will recognize. For example, although steps are presented in a given order above, alternative embodiments may perform steps in a different order. Furthermore, the various embodiments described herein may also be combined to provide further embodiments.

[0164] Implementations of the subject matter and the functional operations described in this patent document can be implemented in various systems, digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Implementations of the subject matter described in this specification can be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a tangible and non-transitory computer readable medium for execution by, or to control the operation of, data processing apparatus. The computer readable medium can be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition of matter effecting a machine -readable propagated signal, or a combination of one or more of them. The term “data processing unit” or “data processing apparatus” encompasses all apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, or multiple processors or computers. The apparatus can include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of them.

[0165] A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00A computer program does not necessarily correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

[0166] The processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform functions by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus can also be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0167] Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, a processor will receive instructions and data from a read only memory or a random access memory or both. The essential elements of a computer are a processor for performing instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks. However, a computer need not have such devices. Computer readable media suitable for storing computer program instructions and data include all forms of nonvolatile memory, media and memory devices, including by way of example semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

[0168] While this patent document contains many specifics, these should not be construed as limitations on the scope of any invention or of what may be claimed, but rather as descriptions of features that may be specific to particular embodiments of particular inventions. Certain features that are described in this patent document in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination.

[0169] Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Moreover, the separation of various system components in the embodiments described in this patent document should not be understood as requiring such separation in all embodiments.

[0170] Only a few implementations and examples are described and other implementations, enhancements and variations can be made based on what is described and illustrated in this patent document.009062.8590. W000\186161420.1

Claims

PCT Patent Application Attorney Docket No. 009062.8590.WO00CLAIMSWhat is claimed is:

1. A device for monitoring brain activity, comprising:a plurality of wires including a plurality of electrodes configured to obtain electroencephalogram (EEG) signals associated with different regions of a scalp, the plurality of electrodes configured to be threaded into a skin layer beneath a surface of the scalp using the plurality of wires to enable positioning of the plurality of electrodes within the skin layer at the different regions, wherein each wire comprises:an electrically conductive inner portion,an insulating layer formed around the electrically conductive inner portion, one or more sections along a length of the wire at which the insulating layer is not present exposing part of the electrically conductive inner portion, wherein two or more sections are spaced apart from one another along the length of the wire according to a predetermined spacing, andan electrode at each of the one or more sections to allow measurement of the EEG signals using the electrically conductive inner portion,wherein the plurality of wires are bundled together such that a first end of each wire is couplable to a tool to enable placement of the plurality of electrodes within the skin layer, and wherein the electrically conductive inner portion is exposed at a second end of each wire to enable acquisition of the EEG signals.

2. The device of claim 1, wherein the skin layer corresponds to an epidermis layer of the scalp.

3. The device of claim 1, wherein the skin layer is beneath a dermis layer of the scalp, wherein the plurality of electrodes is configured to be positioned at the different regions within the skin layer via injection using the plurality of wires.

4. The device of claim 1, wherein the plurality of wires includes at least four wires.

5. The device of claim 1, wherein some or all of the plurality of electrodes include a biocompatible conductive polymer electrodeposited on a surface of the electrode and configured to interface with the scalp.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO006. The device of claim 1, wherein some or all of the plurality of electrodes include a surface modification or a coating.

7. The device of claim 1, wherein the insulating layer comprises a biocompatible material.

8. The device of claim 1, wherein the electrode is customizable in width along the length of the wire based on the one or more portions of the electrically conductive inner portion that are exposed.

9. The device of claim 1, wherein the second end of each wire is configured to couple to a potentiostat, a connector, or a circuit board.

10. The device of claim 1, wherein the plurality of wires that are bundled together form a twisted configuration, and wherein the plurality of electrodes are spaced apart from one another over a length of the twisted configuration according to the predetermined spacing.

11. The device of claim 1 , wherein the electrically conductive inner portion has a diameter of at least 40 microns, wherein the insulating layer has a thickness between 5 to 10 microns, and wherein the one or more sections are between 1 to 3 mm wide along the length of the wire.

12. The device of claim 1, wherein the tool corresponds to a medical needle or an injection tool.

13. A wearable system for monitoring brain activity, comprising:a device according to any one of claims 1-12;a battery configured to supply power to the device; anda wireless circuit comprising:a flexible connector configured to interface with the plurality of electrodes of the device to receive the EEG signals,at least one connector configured to couple the wireless circuit to the battery, at least one processor configured to enable wireless transmission of the EEG signals to an external device, anda multichannel differential amplifier communicatively coupled to the at least one processor and the plurality of electrodes of the device.009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO0014. The wearable system of claim 13, wherein a first end of the flexible connector is coupled to the second end of each wire of the device and a second end of the flexible connector is configured to couple to an input of the wireless circuit.

15. The wearable system of claim 13, comprising a first housing and a second housing configured to couple to the first housing to allow the system to be worn behind an ear, wherein the battery is disposed within the first housing and the wireless circuit is disposed within the second housing.

16. The wearable system of claim 13, wherein the at least one processor comprises an antenna.

17. A method of monitoring brain activity, comprising:using a plurality of wires comprising a plurality of electrodes to position the plurality of electrodes into a skin layer beneath a surface of a scalp such that the plurality of electrodes are positioned within the skin layer at different regions of the scalp, wherein:each of the wires comprises an electrically conductive inner portion and an insulating layer formed around the electrically conductive inner portion,each electrode is associated with one of the wires and is disposed at a section along a length of the wire at which the insulating layer is not present to allow measurement of brain activity using the electrically conductive inner portion, andeach of the different regions is associated with one or more of the electrodes; obtaining electroencephalogram (EEG) signals associated with the different regions of the scalp using at least some of the plurality of electrodes, andproviding the EEG signals as output to enable monitoring of brain activity based on the EEG signals.

18. The method of claim 17, wherein using the plurality of wires comprises injecting or suturing the plurality of electrodes into the skin layer, wherein the skin layer corresponds to an epidermis layer or a dermis layer of the scalp.

19. The method of claim 17, wherein using the plurality of wires comprises:before positioning the plurality of electrodes into the skin layer, twisting the plurality of wires together to form a bundled configuration of the plurality of wires such that the plurality009062.8590. W000\186161420.1PCT Patent Application Attorney Docket No. 009062.8590.WO00of electrodes are spaced apart from one another over a length of the bundled configuration according to a predetermined spacing, andpositioning the plurality of electrodes into the skin later while at least some of the plurality of wires are in the bundled configuration20. The method of claim 17, wherein the plurality of wires includes at least four wires.

21. The method of claim 17, wherein using the plurality of wires comprises coupling a first end of each wire to a device to enable positioning of the plurality of electrodes within the skin layer at the different regions of the scalp.

22. The method of claim 17, wherein some or all of the plurality of electrodes include a biocompatible conductive polymer disposed on a surface of the electrode and configured to interface with the scalp.

23. The method of claim 17, wherein providing the EEG signals as output comprises receiving the EEG signals via a connector coupled to a second end of each wire at which a portion of the electrically conductive inner portion is exposed.009062.8590. WO00X186161420.1

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