Wearable EEG elastic band and porous sponge-based electrode system

Abstract

A conductive sensor lead, comprising: a resilient permeable substrate material; the resilient permeable substrate material comprising a first surface and a second surface, the second surface being configured for contact with a subject, and a solid electrically conductive material disposed within the resilient permeable substrate material so as provide a conductive path between the first surface and the second surface; and a conductive contact associated with the first surface. A system, comprising: a fixture comprising a plurality of sensor leads, a sensor lead comprising (i) a resilient permeable substrate material having first and second surfaces, and (ii) a solid electrically conductive material placed within the resilient permeable substrate material so as to provide a conductive path between the first and second surfaces of the resilient permeable substrate, and the sensor lead configured for electronic communication with a receiver configured to collect a signal from the sensor lead.

Description

25-10873 / 103241.007486 WEARABLE EEG ELASTIC BAND AND POROUS SPONGE-BASED ELECTRODE SYSTEM RELATED APPLICATIONS

[0001] The present application claims priority to and the benefit of United States patent application no.63 / 690,648, "Wearable EEG Elastic Band And Porous Sponge- Based Electrode System" (filed September 4, 2024). All foregoing applications are incorporated herein by reference in their entireties for any and all purposes. . GOVERNMENT RIGHTS

[0002] This invention was made with government support under NS121219 awarded by the National Institutes of Health. The government has certain rights in the invention. TECHNICAL FIELD

[0003] The present disclosure relates to the field of wearable electrodes. BACKGROUND

[0004] Neurological disorders are a significant global health challenge, necessitating advanced methods for non-invasive brain activity monitoring. Scalp electroencephalography (EEG) remains a key tool, yet traditional gel-based electrodes pose comfort and practicality issues. Accordingly, there is a long-felt need in the art for improved electrodes, particularly electrodes useful in EEG applications. SUMMARY

[0005] In meeting the described long-felt needs, the present disclosure provides a conductive sensor lead, comprising: a resilient permeable substrate material; the resilient permeable substrate material comprising a first surface and a second surface, the second surface being configured for contact with a subject, and a solid electrically conductive material disposed within the resilient permeable substrate material so as provide a 4855-6384-0993.125-10873 / 103241.007486 conductive path between the first surface and the second surface; and a conductive contact associated with the first surface.

[0006] Further provided is a method, comprising collecting a signal from a sensor lead according to the present disclosure.

[0007] Additionally disclosed is a system, comprising: a fixture comprising a plurality of sensor leads, a sensor lead comprising (i) a resilient permeable substrate material having first and second surfaces, and (ii) a solid electrically conductive material placed within the resilient permeable substrate material so as to provide a conductive path between the first and second surfaces of the resilient permeable substrate, and the sensor lead configured for electronic communication with a receiver configured to collect a signal from the sensor lead.

[0008] Further provided is a method, comprising collecting a signal from a system according to the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] In the drawings, which are not necessarily drawn to scale, like numerals may describe similar components in different views. Like numerals having different letter suffixes may represent different instances of similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various aspects discussed in the present document. In the drawings:

[0010] FIGs.1A-1E. (FIG.1A) Fabrication of dry Ti3C2TxMXene EEG electrodes. (FIG.1B) Axial expansion of the PVA templates dip-coating in the Ti3C2Txdispersion. (FIG.1C) SEM images of PVA discs before and Ti3C2Txcoating (100x magnification). (FIG.1D) Raman spectra of PVA discs, Ti3C2Txfilms drop cast on glass, and Ti3C2Tx-PVA electrodes. (FIG.1E) Fully assembled dry Ti3C2Txelectrodes.

[0011] FIGs.2A-2C (FIG.2A) Schematic of the custom 3D printed connector holders with dimensions. (FIG.2B) Photograph of the holders with attached electrodes and connectors. (FIG.2C) Left: 10-20 EEG headsets with 21 electrodes on defined anatomical landmarks marked on the channel mapping schematics; right: 8-electrode headband with channel mapping.

[0012] FIGs.3A-3E (FIG.3A) Average impedance modulus and phase spectra for 10 electrodes (N = 5 participants). (FIG.3B) Average 10 Hz impedance of dry Ti3C2Tx- 2 - 4855-6384-0993.125-10873 / 103241.007486 and gelled electrodes on agarose phantoms. (FIG.3C) 10 Hz impedance throughout 5 cycles of compression (N = 5 electrodes). (FIG.3D) Load and extension curves for 50 compression cycles. (FIG.3E) Average hysteresis loss of 5 different dry Ti3C2Txelectrodes over 50 compression cycles.

[0013] FIGs.4A-4F. (FIG.4A) Schematic configuration of the dry Ti3C2Txand Ag / AgCl cup electrode positions. (Reference and ground electrodes on the mastoid, not shown). (FIG.4B) Experimental protocol. (FIG.4C) Representative of EEG on dry Ti3C2Txand adjacent Ag / AgCl electrodes. (FIG.4D) Pearson correlation for electrode pairs across brain regions (calculated across all 5 participants). (FIG.4E) Topographical maps of EEG power distribution at 20 Hz at resting state Vs. stimuli for all 5 participants (Subject 1 – S1, Subject 2 – S2, etc.). (FIG.4F) Representative average (top) PSD and (bottom) 20 Hz SNR during resting and stimulus recordings across (left) all occipital / parietal MXene electrodes (P3, P4, O1, O2, Pz) and (right) the most proximal gelled electrode at O2 in subject 5 (S5).

[0014] FIGs.5A-5B. (FIG.5A) Schematics of the setup and task for clinical EEG recordings with the 8-channel dry Ti3C2Txelectrode headband. (FIG.5B) (From left) Representative 4 s timeseries (bi-polar montage), PSD, and spectrogram of the EEG recorded with (top) dry Ti3C2Txand (bottom) Ag / AgCl cup electrodes for participant S3. (PSD for all other participants are in FIG.14).

[0015] FIGs.6A-6E. (FIG.6A) Schematics of the setup and study design for the wireless EEG recordings with the 8-channel dry Ti3C2Txelectrode headband in ambulatory settings. (FIG.6B) Representative timeseries of different EEG bands collected with dry Ti3C2Txand Ag / AgCl electrodes in F7 during walking. (FIG.6C) Average alpha band SNR for dry Ti3C2Txand Ag / AgCl electrodes in different states (i.e., sitting, standing, and walking). (FIG.6D) Area under the curve (AUC) of the power in alpha band, showing the alpha-band activity depression during walking. (FIG.6E) Average power spectra of all dry Ti3C2Txelectrodes on the headband (n=8) for a representative subject in different states.

[0016] FIGs.7A-7B. (FIG.7A) SEM images of PVA discs before MXene and after and after MXene absorption (~700 X magnification). (FIG.7B) EDX analysis of inked MXene + PVA pillars.

[0017] FIG.8. EDX analysis of uncoated PVA pillars. - 3 - 4855-6384-0993.125-10873 / 103241.007486

[0018] FIG.9. Compression of MXene + PVA electrodes (left) dry and (right) moistened.

[0019] FIG.10. Skin preparation protocol for (top): dry MXene and (bottom): gelled electrodes

[0020] FIG.11. Ag / AgCl electrodes used for the 4.5 impedance tests in agarose phantoms: (top) 3mm gelled cup electrode, (bottom) 20mm gelled disc electrode.

[0021] FIG.12. Average 10 Hz impedance over 4.5 hours on agarose phantom for dry Ti3C2Txand gelled Ag / AgCl (disc and cup) electrodes (n=5 electrodes of each type).

[0022] FIG.13. Average SSVEP response during resting and stimulus recordings across occipital / parietal electrodes (P3, P4, O1, O2, Pz) for subjects S1 to S4. Resting state in red, SSVEP in blue.

[0023] FIGs.14A-B. (FIG.14A) Power spectra for participants S1, S2, S4, and S5 during eyes closed task of the clinical EEG study. (FIG.14B) Pearson’s correlation of the PSD of dry Ti3C2Txand gelled cup Ag / AgCl electrodes at different locations for all 5 participants.

[0024] FIG.15. Average power spectra for all electrode during each task for each subject, each row is a subject.

[0025] FIG.16. Demographic information for participants across all studies using MXene +PVA pillar electrodes.

[0026] FIG.17. (A) TMS-induced displacement and (B) Temperature and voltage measurement setups. (C) Displacement from a single pulse stimulation at varying TMS machine output (n=1 per stimulation condition). (D) Temperature profiles measured before, during, and after (left) 10 Hz TMS stimulation at 80% output and (right) 50 Hz theta burst at 45% output (n=2 for stimulation condition). (E) Biphasic voltage pulses on the dry Ti3C2Txelectrodes with (F) peak-to-peak amplitudes and (G) resulting charge densities (n=3 for stimulation condition). All percentages denote the TMS machine output.

[0027] FIG.18. (A) Schematics of the dry Ti3C2Txand Ag / AgCl cup electrode positions. (Reference and ground electrodes on the mastoids, not shown). (B) Schematics of the visual stimulation presentation setup. (C) Representative 10 s of EEG on dry Ti3C2Txand adjacent Ag / AgCl electrodes. (D) Pearson correlation for electrode pairs across brain regions (calculated across all 5 participants). (E) Representative average (top) - 4 - 4855-6384-0993.125-10873 / 103241.007486 PSD and (bottom) 20 Hz SNR during resting and stimulus recordings across (left) all occipital / parietal MXene electrodes (P3, P4, O1, O2, Pz) and (right) the most proximal gelled electrode at O2 in subject 5 (S5). (F) Topographical maps of EEG power distribution at 20 Hz at resting state Vs. stimuli for all 5 participants (Subject 1 – S1, Subject 2 – S2, etc.). DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0028] The present disclosure may be understood more readily by reference to the following detailed description of desired embodiments and the examples included therein.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict, the present document, including definitions, will control. Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting.

[0030] The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

[0031] As used in the specification and in the claims, the term "comprising" can include the embodiments "consisting of" and "consisting essentially of.” The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that require the presence of the named ingredients / steps and permit the presence of other ingredients / steps. However, such description should be construed as also describing compositions or processes as "consisting of" and "consisting essentially of" the enumerated ingredients / steps, which allows the presence of only the named ingredients / steps, along with any impurities that might result therefrom, and excludes other ingredients / steps.

[0032] As used herein, the terms “about” and “at or about” mean that the amount or value in question can be the value designated some other value approximately or about - 5 - 4855-6384-0993.125-10873 / 103241.007486 the same. It is generally understood, as used herein, that it is the nominal value indicated ±10% variation unless otherwise indicated or inferred. The term is intended to convey that similar values promote equivalent results or effects recited in the claims. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but can be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about” or “approximate” whether or not expressly stated to be such. It is understood that where “about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.

[0033] Unless indicated to the contrary, the numerical values should be understood to include numerical values which are the same when reduced to the same number of significant figures and numerical values which differ from the stated value by less than the experimental error of conventional measurement technique of the type described in the present application to determine the value.

[0034] All ranges disclosed herein are inclusive of the recited endpoint and independently of the endpoints. The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value; they are sufficiently imprecise to include values approximating these ranges and / or values.

[0035] As used herein, approximating language can be applied to modify any quantitative representation that can vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as “about” and “substantially,” may not be limited to the precise value specified, in some cases. In at least some instances, the approximating language can correspond to the precision of an instrument for measuring the value. The modifier “about” should also be considered as disclosing the range defined by the absolute values of the two endpoints. For example, the expression “from about 2 to about 4” also discloses the range “from 2 to 4.” The term “about” can refer to plus or minus 10% of the indicated number. For example, “about 10%” can indicate a range of 9% to 11%, and “about 1” can mean from 0.9-1.1. Other meanings of “about” can be apparent from the context, such as rounding off, so, for example “about 1” can also mean from 0.5 to 1.4. - 6 - 4855-6384-0993.125-10873 / 103241.007486

[0036] Further, the term “comprising” should be understood as having its open- ended meaning of “including,” but the term also includes the closed meaning of the term “consisting.” For example, a composition that comprises components A and B can be a composition that includes A, B, and other components, but can also be a composition made of A and B only. Any documents cited herein are incorporated by reference in their entireties for any and all purposes.

[0037] Any embodiment or aspect provided herein is illustrative only and does not limit the scope of the present disclosure or the appended claims. Any part or parts of any one or more embodiments or aspects can be combined with any part or parts of any one or more other embodiments or aspects.

[0038] This disclosure introduces a novel dry EEG technology utilizing porous polyvinyl acetate (PVA) pillars coated with Ti3C2TxMXene, a two-dimensional transition metal carbide known for its high conductivity and biocompatibility. Here we developed a scalable fabrication protocol for these electrodes and integrated them into custom headcaps designed for both limited montage and full scalp recordings. Electrochemical impedance measurements on human participants and conductive phantoms showed our Ti3C2TxMXene electrodes maintained low impedance comparable to gel-based electrodes at initial use and over extended periods. Mechanical testing revealed the electrodes’ resilience to compression, ensuring consistent performance. We validated our electrodes and headcaps in various settings, including clinical, research, and ambulatory environments, demonstrating the electrodes' capability to capture high-quality EEG signals, comparable to traditional methods, while significantly enhancing user comfort. This technology aims to improve EEG accessibility and usability, catering to diverse hair types and application needs. Our findings suggest that Ti3C2TxMXene-based dry EEG electrodes are a viable alternative to gel-based systems, with potential for broad application in both clinical diagnostics and neurological research.

[0039] Introduction

[0040] Neurological disorders are the second leading causes of death and present a significant challenge to public health. To make advances toward diagnosing, preventing, or treating such disorders clinicians and researchers have been making efforts to study the brain’s dynamics in a minimally invasive manner. In order to gain deeper insights into brain activity and function non-invasively, clinicians and researchers rely on - 7 - 4855-6384-0993.125-10873 / 103241.007486 electroencephalography or EEG to capture signals using conductive electrodes placed on the surface of the skin.

[0041] There are a variety of different options for electrodes and methods that can be used to obtain EEG signals. One option includes the use ear EEG which involves the placement of an electrode in or around the ear. These types of electrodes offer user a high level of comfort and mobility and may even be less susceptible to signal artifacts that are often prominent in traditional scalp EEG recordings (facial muscle movements, eye blinks, etc.). The placement of ear EEG electrodes tends to work with a variety of users since they do not require placement on the scalp which can be challenging depending on participants’ hair pattern and require shaving or parting the hair in recording areas to achieve good contact.

[0042] While ear EEG offers many advantages and is relatively simple in its recording setup, it is also has its limitations when it comes to monitoring. Ear EEG electrodes provide limited spatial resolution as they do not cover a variety of brain regions in comparison to standard scalp monitoring setups. Individual ear anatomy also tends to vary quite a bit from person to person in comparison, making it difficult to achieve optimal placement and contact for all users with one device form. Additionally, it may be challenging to interpret recordings obtained from ear EEG as they often consist of overlapping signals and information from different brain regions, which can complicate analysis.

[0043] Alternatively, standard scalp EEG has been a reliable and widely used method used for years to accurately obtain signal activity from a variety of regions. Scalp EEG has a high temporal resolution and greater spatial sampling compared to ear EEG as it can span the whole head. It is also versatile in its applications and used to study cognitive and neurological functions (epilepsy, sleep disorder, attention disorder, etc.). Scalp EEG can be used for a variety of different age ranges and offers clinicians and researchers a way to monitor brain activity in real time. There are several types of electrodes that can be used for scalp EEG. Traditionally in clinical settings Ag / AgCl or metal (gold (Au), tin (Sn) and, platinum (Pt)) cup electrodes are used with a conductive gel to record EEG from the scalp. This type of electrode set up is referred to as a ‘wet electrode’. - 8 - 4855-6384-0993.125-10873 / 103241.007486

[0044] While the conductive gel and pastes offer enhanced electrode skin contact and low interface impedance which in return enables high signal quality recordings, they also have several limitations. The gels and pastes needed for these types of electrodes leave a residue in users’ hair which can be uncomfortable and vigorous multistep skin preparation involving abrasive pastes is required for electrode placement and maintaining contact with the scalp. The placement of these types of electrodes is also time consuming and requires and expert technician. Scalp EEG electrodes are placed according to the internationally recognized 10-20 system, which requires specific spacing and locations that span the entire scalp. Technicians undergo extensive training to properly identify and place electrodes according to these standardized locations. Furthermore, gelled cup electrodes often do not work well with diverse hair types, which affects the quality of signals recorded and, consequently, the interpretation of such data. This limitation can lead to disparities in diagnosis, care, and inclusion for certain demographic groups in studies and investigations that rely on this data.

[0045] To circumvent some of these issues there have been efforts to transition to dry gel free electrodes. Dry electrodes measure bioelectrical activity without the use of conductive gels or pastes. This can be particularly advantageous when situations require quick setup or even to ease user hesitation when gels and pastes are not wanted. Without pastes and gels, it is often difficult to maintain low interface impedance and dry electrodes must employ other methods to improve interfacing with the skin. Heavy bulk headsets that apply high pressure are typically employed to maintain electrode contact with the scalp. These headsets must maintain adequate pressure while still remaining comfortable to users.

[0046] Dry EEG headsets can often be re-used and are convenient for unmonitored use and they don’t require expert knowledge for placement. Many dry electrode headsets are still quite uncomfortable to users as they do not use flexible soft materials which can be irritating with long term use and during sleep monitoring conditions. Additionally, headcaps and connectors for these electrodes may face difficulties in integrating with existing monitoring equipment and data acquisition systems, as they come with their own software and systems that must be used. Commercially available dry electrode headsets also either come in a limited montage configuration or a full scalp montage configuration, where there are diminished - 9 - 4855-6384-0993.125-10873 / 103241.007486 opportunities for custom montages or recording set ups. As for materials and the geometry used for dry sensing, some techniques used to improve interface impedance include increasing the surface area of electrodes to increase the electrode skin surface contact area, using new conductive materials and specialized coatings, or using multi-pin geometries to contact the scalp through the hair.

[0047] Dry electrodes can be manufactured using commonly used metals such as Ag / AgCl, Au, or Pt. These metals are durable and have excellent conductivity however they require specific design modification to ensure effective contact with the scalp and can be uncomfortable to wear over long period of time. Some metals such as Au, can also be costly to use in manufacturing while others tend to have higher impedances during recording. Conductive polymers and hydrogels using materials such as PEDOT can also be used to create dry electrodes. These polymers are more flexible than traditional metal electrodes and allow for greater conformability with the scalp while maintaining good conductivity.

[0048] Unfortunately, some of these conductive polymers are moisture sensitive and tend to degrade in performance over time with wear on the scalp. Hydrogels may not be as breathable as necessary for long term wear and may require careful cleaning and reapplication or adjustment of the gel. Additionally the fabrication process for hydrogel electrodes can be complicated requiring precise control over polymerization and gel formation, which can cause issues in large scale manufacturing.

[0049] Two-dimensional materials such as graphene and MXenes are promising due to their high conductivity and biocompatibility. Graphene excels in flexibility and mechanical strength but poses challenges in integration into large-area or wearable systems, due to complicated transfer processes and integration into devices.

[0050] MXene, a two-dimensional transition metal carbine characterized by 1nm thick flake, has proven itself as a promising candidate for developing the next generation of novel neural interfaces. he material’s hydrophilic solution processable nature lends to its biocompatibility and use in scalable processing and manufacturing techniques. The material is also highly conductive, up to 20,000 S / cm, making it appealing for use in bioelectronics.

[0051] Thus, a need presents itself for improved Ti3C2TxMXene electrode technology using more scalable manufacturing techniques, with improved geometry while - 10 - 4855-6384-0993.125-10873 / 103241.007486 maintaining low impedance and good scalp contact through regions with dense hair, while prioritizing user comfort. It is important that this technology also caters to a diverse range of hair types to uphold inclusivity in research and clinical procedures.

[0052] Here we demonstrate the development of porous sponge like polyvinyl acetate (PVA) pillars based on Ti3C2TxMXene for dry EEG recordings. We have developed a high throughput fabrication protocol for manufacturing of soft low impedance dry electrodes. We also show development of two custom headcaps for limited montage and full scalp recording potential as well as validate our technology in a variety of recording environments: clinical, research, ambulatory settings.

[0053] Results and Discussion

[0054] Rapid, scalable fabrication of dry, 3D Ti3C2TxMXene electrodes

[0055] Results from exemplary, non-limiting Ti3C2TxMXene electrodes are provided herein. It should be understood, however, that the disclosed technology is not limited to these specific electrodes.

[0056] To form the 3D electrode templates, we start from an absorbent sheet of hydroxylated polyvinyl alcohol (PVA, Medtronic Kennedy Sinus-Pak) and cut out 8 mm disks (FIG.1A). We chose PVA because it is biocompatible, hydrophilic, and it is already commonly used in different medical devices, including contact lenses, arterial grafts, wound dressing, osteochondral grafts. It is worth noting that this process can be implemented on any porous aerogel and scaled up with die or laser cutting of the template materials. The PVA disks are then dip-coated in an aqueous dispersion of Ti3C2TxMXene at the concentration of 20 mg / mL. Owing to their hydrophilic nature, upon water absorption the PVA aerogels expand axially from their initial disk structure (height: ~ 1 mm) to a cylindrical shape (height: ~8 mm in height), while the diameter remains unchanged (FIG.1B). The final electrode’s sponge like properties present as a firm structure initially but softens in presence of moisture (absorbing approximately 1ml of liquid) (FIG.1E and FIG.3). Scanning electron microscopy imaging of the PVA disks (SEM, FIG.1C) shows the expansion and increase in porosity of the PVA matrix (initial pore size: ~70 µm, final pore size: ~200 µm) upon absorption of the aqueous Ti3C2Txdispersion, with Ti3C2Txflakes homogeneously coating PVA (FIG.7). Energy-dispersive X-ray spectroscopy (EDX) analysis of the Ti3C2Tx-PVA electrodes shows predominant -Ti and -C as well -O peaks (Weight %: Ti: 28.2, C: 30.71, O: 39.93), alongside with - 11 - 4855-6384-0993.125-10873 / 103241.007486 negligible amount of -F and -Cl (Weight %: F: 0.16, Cl: 0.74) surface groups from the etching phase of the Ti3C2Txsynthesis. The % -O content of the Ti3C2Tx-PVA electrodes (FIG.8) is comparable to that of pristine PVA (Weight % O - 47.07), which indicates no oxidative damage to Ti3C2Txfrom the fabrication process. Raman spectra of the Ti3C2Tx- PVA electrodes excited with a 785 nm laser show the out-of-plane A1gvibration modes of Ti, C, and O atoms at ~200 cm-1and of the C atoms at ~ 720 cm-1(FIG.1D). These characteristic Raman modes of Ti3C2Txcan be also observed on dry Ti3C2Txfilms on glass substrates, but not on the PVA templates, confirming that the templates are uniformly covered by Ti3C2Txflakes and the preservation of Ti3C2Txquality. Finally, after drying the Ti3C2Tx-PVA electrodes at room temperature for 45 minutes, Ag / AgCl button snap connectors are attached with Ag epoxy, followed by a final 10-min curing step in the oven at 80 °C. The total manufacturing time for a batch of 10 electrodes is < 1 hour, including drying steps.

[0057] Fabrication of dry MXene EEG headsets

[0058] In standard clinical brain monitoring and diagnostics, a set of 21 EEG electrodes are placed at defined cranial landmarks and at specific relative distances. This internationally recognized configuration, known as the 10-20 system, ensures consistent and repeatable placement of the electrodes electrode across subjects, scalp sizes, and clinical centers. To replicate this standard configuration, we built two custom headsets using flexible elastic bands with 21 electrode connectors placed in correspondence of the scalp locations in the 10-20 EEG system. The connectors consist of snap-on leads that are held in place by custom 3D-printed holders, which allow keeping the leads securely in place even during movement and easily removing them as needed (FIG.2A-C).

[0059] Using button-snaps for the EEG connectors headsets offers several key advantages. First, these connectors are standard in EEG systems and are compatible with several commercial EEG amplifiers (both for clinical and research use), thus simplifying the integration of these novel dry electrodes with existing equipment and workflows. Second, these connectors are easy to use and allow for quick and secure electrode placement / removal, thus providing the robustness and efficiency required in clinical settings. Finally, the versatility of these connectors – also available in MRI-compatible versions – enables using our dry MXene EEG electrodes in different research and clinical scenarios, thus making them cost-effective and reducing the burden of adoption. - 12 - 4855-6384-0993.125-10873 / 103241.007486 Leveraging the versatility of the electrode and headset fabrication, we also designed a reduced-montage EEG headband consisting of 8 electrodes placed at defined anatomical locations along the scalp circumference (Fp1, Fp2, F7, F8, T7, T8, P7, and P8) (FIG. 2B,C).

[0060] Similar to the full-head design, in the here the electrodes are secured to the headband with 3D-printed holders and plugged into the amplifier via flat snap connector leads (FIG.2B). The headband and full-scalp EEG cap are fabricated from an elastic fabric and equipped with an adjustable band to secure the headsets to different head sizes and ensure that the electrodes can safely contact the scalp. The headset designs also allow for easy access to electrode sites for hassle-free access to the scalp and replacement / adjustment of the electrodes.

[0061] Electrochemical and mechanical characterization of dry Ti3C2TxEEG electrodes.

[0062] The electrode-skin interface impedance represents the resistance to charge and signal transfer at the interface between an EEG electrode and the skin. Such interfacial impedance is critical for the quality, fidelity, and stability of the EEG signal. Some of the key factors affecting impedance are the electrode material, the quality of contact between the skin and the electrode, skin conditions and preparation, and the application of conductive gels and adhesives. Compared to conventional gelled electrodes, dry electrodes often exhibit higher impedance (i.e. > 50 kΩ at 10 Hz), and have an unstable contact with the scalp as they do not rely on conductive gels or pastes. Such high impedance and contact instability can compromise signal fidelity, increase noise, and introduce artifacts. To measure the electrode-skin impedance of dry Ti3C2TxEEG electrodes, we conducted electrochemical impedance spectroscopy (EIS) analysis on the scalp of n=5 participants. For each participant, we prepped the skin with a simplified non-irritating preparation protocol (FIG.10), then we acquired EIS with dry Ti3C2Txelectrodes in two different locations: 1) on the lateral forehead Fp1, a region with no hair, and 2) on the temporal region T8, a site with hair. We used an Ag / AgCl reference electrode placed on the mastoid. FIG.3A shows the average EIS spectra in the 1-105Hz range for the 10 electrodes (n=2 for each participant). We found that at 1-100 Hz – the relevant EEG frequency band – the impedance modulus of the dry Ti3C2TxEEG electrodes shows a frequency-independent response with a phase shift of < 5°. This indicates that the dry - 13 - 4855-6384-0993.125-10873 / 103241.007486 Ti3C2Txelectrodes response is predominantly resistive and that they can collect and transmit the EEG signal without introducing phase distortions. At 10 Hz, the average impedance across our cohort of participants with a diversity of skin types was 2.1 ± 1.8 kΩ. This value is in agreement and well within the range of what is considered acceptable for clinical-grade gelled EEG electrodes for human use (i.e., < 10 kΩ). To benchmark the performance and impedance stability of dry Ti3C2Txelectrodes over time, we collected EIS continuously for 4.5 hours on an agarose phantom and compared with two different types of Ag / AgCl gelled electrodes of common use: 20mm discs and 3mm cups (FIG.11). Ag / AgCl disk electrodes have a larger, flat surface and are often used in clinical and research settings for short EEG exams (20 min-1 hour). Ag / AgCl cup electrodes are smaller and concave and are designed to be filled with conductive gels for long-term monitoring (e.g., inpatient continuous EEG in the epilepsy monitoring unit). At the beginning of the study the 10 Hz impedance of dry Ti3C2Txelectrodes was 0.29 ± 0.03 kΩ at 10 Hz, which was comparable to the starting impedance of both gelled disc (0.21 ± 0.02 kΩ) and cup electrodes (0.18 ± 0.04 kΩ) (FIG.3B). The impedance of dry Ti3C2Txelectrodes increased by ~0.2 kΩ for the first 2 hours, then stabilized and remained unchanged for the following 2.5 hours (ZfinalTi3C2Tx0.48 ± 0.07 kΩ), while the impedance of both types of gelled electrodes remained essentially unchanged for the entire duration of the study (Zfinaldisc: 0.20 ± 0.03 kΩ , Zfinalcup: 0.16 ± 0.03 kΩ) (FIG.12).

[0063] In addition to establishing a stable contact with the scalp, EEG electrodes need to be mechanically robust and sustain the pressure that is applied during placement and removal. This is a particularly important requirement for dry Ti3C2Txelectrodes due to their foam-like porous and compressible structure characterize. Here we compressed n=5 Ti3C2Txelectrodes by 80% of their axial length (~6mm) with a 15 N load cell and collected EIS on an agarose after each cycle of compression / extension. After 5 cycles the 10 Hz impedance of Ti3C2Txshowed a statistically significant increase from its initial value (p = 0.03, Mann-Whitney test: 0.05 significance level, FIG.3C), but still remained within the acceptable limit of <10 kΩ. However, after 50 compression cycles the Ti3C2Txelectrodes retain the ability to extend back to the original height and did not show any visible mechanical degradation (FIG.3D). This is verified by a hysteresis loss of less than 5% across over 50 cycles as calculated from the measured load-extension curves (FIG. 3E). Such a low hysteresis loss here indicates that our Ti3C2TxMXene electrodes have a - 14 - 4855-6384-0993.125-10873 / 103241.007486 stable energy dissipation, behave elastically, and maintain their integrity under 50 cycles of repeated loading and unloading.

[0064] Full scalp EEG recording with dry MXene electrodes

[0065] Consistent and comfortable placement of the electrodes on the scalp are key to ensure repeatability, reliability, and quality of EEG recordings. Ag / AgCl gelled electrodes are typically used for full scalp EEG, since the presence of the gel layer between the electrodes and the scalp ensures proper adhesion, while minimizing subject- to-subject scalp variability and interface impedance. Due to the lack of such gels, consistent and comfortable placement of dry EEG is significantly more challenging, and typically application of mechanical pressure is required to maintain adequate contact along all scalp planes for stable EEG recordings. Here we sought to validate and benchmark the 21-channel dry Ti3C2TxEEG headset (i.e., 10-20 system) against commercial Ag / AgCl gelled electrodes during common tasks performed in brain computer interface (BCI) paradigms. In these studies we asked participants (n=5) to wear the headcap of dry Ti3C2Txelectrodes arranged according to the 10-20 system, and then placed 3 additional Ag / AgCl cup electrodes (3 mm diameter, FIG.11) adjacent to 3 dry electrodes for direct comparison of signals across scalp sites with varying levels of hair density: Frontal (Fp1), Motor (C3), and Occipital (O2) (FIG.4A). Reference and ground electrodes were placed on the mastoid. After placing the electrodes, we collected 2 minutes of resting state EEG, then asked participants to observe a screen with a 20 Hz flashing stimulus source (FIG. 4B). These flashing visual stimuli are expected to elicit a 20 Hz steady state visual evoked potential (SSVEP) response, which has been accepted for BCIs and noted for its accuracy.

[0066] From the signal quality standpoint, we observed that EEG signals collected on dry Ti3C2Txelectrodes were highly comparable to adjacent Ag / AgCl sites, as also indicated by a high Pearson correlation throughout the whole recording session (i.e., resting state + SSVEP task, Frontal: 0.895 ± 0.059, Motor: 0.929 ± 0.047, Occipital: 0.989 ± 0.011; n = 5 electrode pairs; FIG.4C,D). In the SSVEP task, across all subjects we were able to identify the expected increase in the power spectral density (PSD) and SNR of the EEG collected on dry Ti3C2Txelectrodes centered at the frequency of the visual stimulation (i.e., 20 Hz, FIG.4F and FIG.13). (FIG.4E and FIG.13). Specifically, we found that the increase in SNR at 20 Hz compared to resting states of electrodes in the region of interest (P3, P4, Pz, O1, O2) is significant across all participants (p = 0.01 ± - 15 - 4855-6384-0993.125-10873 / 103241.007486 0.01). This increase in 20 Hz response is also observed on the most proximal gelled Ag / AgCl electrode placed in the occipital region. Topographical maps of the 20 Hz power distribution on the scalp built from the dry EEG recordings (FIG.4F) show that the 20 Hz activity is spatially localized on the electrodes in the occipital region, which are the most proximal to the visual cortex. Overall, these results demonstrate the ability to record full- scalp EEG with a 10-20 dry Ti3C2Txheadset designed to optimize scalp contact and user comfort. Furthermore, dry Ti3C2Txfull-scalp headsets can collect EEG signal of the same quality of similar quality and reliability of state-of-the-art commercial Ag / AgCl electrodes, and capture relevant physiological for cognitive and BCI research applications.

[0067] Clinical EEG recordings with the 8-channel dry Ti3C2Txelectrode headband

[0068] Reduced montage configurations are becoming increasingly popular for rapid bedside and at-home EEG monitoring. Specific to clinical settings, reduced montage EEG has proven useful for quick diagnostics and detection of slowing brain patterns in epilepsy patients. With these scenarios in mind we sought to validate the 8-channel dry Ti3C2TxEEG headband in a relevant clinical scenario. Also in these studies, we benchmarked our dry electrodes against standard clinical gelled electrodes. We recruited and consented n=5 patients who were scheduled for a routine EEG exam in the outpatient EEG clinic of the Hospital of the University of Pennsylvania and conducted the study with the dry Ti3C2Txheadband prior to their EEG visit. After placing the dry EEG headband, we asked patients to open and close their eyes for a few minutes at a time as a part of standard clinical protocols and collected the EEG (FIG.5A). We designed the eyes open / closed tasks to match the clinical protocol, which allowed us to compare the EEG collected in the research (i.e., dry Ti3C2Tx) and clinical (i.e., Ag / AgCl cup) sessions on the same patient. Comparison of the signals shows that also in clinical settings the EEG on dry Ti3C2Txelectrodes is highly comparable to gelled Ag / AgCl, the current standard of care (FIG.5B). Then, we looked at the posterior dominant rhythm (PDR) that is presented as an increase in the power of the EEG at 8-12 Hz in the eyes closed state. The PDR is typically observed in the occipital regions of the brain, is a key component of the resting EEG that reflects the normal cortical activity when the individual is awake and relaxed. Measuring PDR is crucial for several reasons: 1) PDR is a baseline indicator of cortical function, 2) it helps assessing the integrity of the sensory and cognitive processing areas, - 16 - 4855-6384-0993.125-10873 / 103241.007486 and 3) it provides insights into overall brain health. Deviations or abnormalities in PDR can be indicative of various neurological conditions, including epilepsy, sleep disorders, and cognitive impairments. Here, we during the eyes-closed task we detected the PDR in the EEG acquired with both sets of electrodes (FIG.5B and FIG.14). Looking at the PSD of the EEG, we also found the expected spatial distribution of the PDR response, with posterior electrodes (i.e., T-P bipoles) having a higher PDR response compared to anterior electrodes (i.e., Fp-F). To compare the similarity (or lack thereof) of the EEG collected on the each of the dry Ti3C2Txelectrodes to that on the Ag / AgCl in the corresponding location, we calculated the Pearson’s correlation of the power spectra densities and found that the signals were highly correlated in all the locations and across all the 5 patients (>0.8, FIG.14). Furthermore, a board-certified neurologist read the EEGs collected with both electrode types, confirming that all key EEG features seen on the clinical recordings (i.e., PDR) were also present on the recording collected with dry Ti3C2Txelectrodes and that in some cases the Ti3C2TxMXene and clinical recordings were indistinguishable.

[0069] Ensuring that EEG data obtained from Ti3C2Txelectrodes is qualitatively interpretable by a clinician on their clinical EEG visualization software confirms that 1) the signal collected on our novel dry electrodes accurately represents the brain activity, and 2) the dry EEG headband can be seamlessly integrated with current clinical software and workflows. Validating that the novel electrodes provide data compatible with clinical standards is essential for their acceptance and adoption in clinical practice. Clinicians qualitatively read EEG by analyzing waveform patterns, frequencies, and rhythms to identify normal and abnormal brain activity. They assess event-related potentials, spatial distribution of electrical activity, and temporal changes in the signal to diagnose neurological conditions and evaluate brain function.

[0070] Wireless EEG recordings in dynamic settings

[0071] Another area of clinical and research interest lies in realizing the ability to make dry EEG technology that can be deployed in remote settings or used for ambulatory home monitoring. Remote and ambulatory home monitoring is pivotal in enabling continuous, non-invasive brain activity tracking in settings outside of traditional clinical environments. This capability is critical for long-term monitoring of neurological conditions, early diagnosis, and real-time management, especially for patients in remote areas or those requiring frequent assessments. - 17 - 4855-6384-0993.125-10873 / 103241.007486

[0072] Gelled electrode technology presents challenges in these environments that limit its use in these settings. Gel-based electrodes require the application of conductive gel, which can dry out over time, leading to poor signal quality and the need for frequent reapplication. Additionally, the setup process is time-consuming, often requiring trained personnel, making it impractical for remote or unsupervised use.

[0073] Dry electrodes are ideal for remote, unsupervised use because they don't require conductive gels, simplifying setup and maintenance. Their ease of use and comfort make them more practical for long-term monitoring in non-clinical environments, allowing users to apply them independently and reliably.

[0074] One of the key challenges in developing dry EEG systems is ensuring that the electrodes maintain stable contact with the scalp without shifting, as even slight movements can introduce significant motion artifacts that degrade signal quality. Achieving consistent electrode-skin contact in a comfortable, non-invasive manner, especially during long-term monitoring or in ambulatory settings, is essential to minimize these artifacts and ensure reliable data acquisition. Here we demonstrated the use of our electrodes and limited montage band for ambulatory and wireless monitoring.

[0075] To mimic movements that may occur in ambulatory EEG applications, we captured EEG while participants were freely moving, walking at their own pace. We asked participants to sit, stand, and walk for up to 2 minutes with their eyes closed, while we wirelessly recording EEG (FIG.6A). These tasks should show a decrease in alpha rhythm (8-12 Hz) in movement states compares to resting (standing and sitting states) due desynchronization that occurs during recruitment of brain regions during motor-based tasks. We included a comparison Ag / Agl electrode next to electrode location F7 and found that during all tasks including walking, we were able to record EEG signals similarly to our comparison gelled electrode (FIG.5B,C).

[0076] During walking we also see the expected decrease in alpha activity, as measured by area under the curve (AUC) value of the alpha power peak, in comparison to stationary recordings (FIG.5D,E and FIG.15). Our data indicates reliable ability to record activity while participants are moving, showing potential for ambulatory EEG monitoring needs.

[0077] Conclusions - 18 - 4855-6384-0993.125-10873 / 103241.007486

[0078] In this study, we successfully develop a novel dry electrode technology based on porous polyvinyl acetate (PVA) pillars coated with Ti3C2TxMXene flakes for electroencephalography (EEG) recordings. We were able to develop a rapid and scalable fabrication process, allowing for high throughput manufacturing of soft, low impedance dry electrodes. The resulting electrodes exhibit excellent electrochemical stability and maintain low impedance values (<10 kΩs) with minimal skin prep and no gel, crucial for comfortable high-quality EEG recordings.

[0079] We validated the performance of these electrodes using custom-designed headsets tailored for both limited montage and full scalp recordings across three different recording environments, setups, and interfaced with different acquisitions systems (Table 1). Table 1. Recording information and parameters for each of the three studies.

[0080] The headsets provide a comfortable and adjustable fit, accommodating various head sizes and hair types, ensuring inclusivity in clinical and research applications. Mechanical testing demonstrated that the electrodes withstand multiple cycles of compression without significant loss of functionality, as indicated by low hysteresis loss, highlighting their robustness for repeated use.

[0081] Our in vivo validation confirmed that the Ti3C2TxMXene electrodes can reliably capture EEG signals comparable to traditional gel-based Ag / AgCl electrodes. The high correlation in recorded signals and the ability to detect expected physiological features, such as steady-state visual evoked potentials (SSVEP) and posterior dominant rhythm (PDR), underscores the efficacy of our electrodes in both full and limited montage configurations.

[0082] Additionally, we demonstrate the use of the disclosed technology in ambulatory and wireless EEG monitoring, with the electrodes maintaining reliable signals - 19 - 4855-6384-0993.125-10873 / 103241.007486 during dynamic tasks such as walking. The disclosed technology can be effectively used in remote settings or for continuous monitoring in everyday environments, providing new opportunities for the management and study of neurological disorders.

[0083] In conclusion, the exemplary Ti3C2TxMXene-coated PVA pillar electrodes represent a significant advancement in EEG technology, wherein we created a solution for comfortable low impedance EEG monitoring that works with a variety of participants with different demographics and hair types (FIG.16). They offer a comfortable, versatile, and scalable solution for both clinical and research applications, addressing many of the limitations associated with traditional gel-based and dry electrodes.

[0084] Methods and Materials

[0085] Fabrication of dry Ti3C2TxMXene electrodes

[0086] An 8 mm biopsy punch was used to cut circular discs out of a sheet of hydroxylated poly-vinyl acetate (PVA) (Merocel Kennedy Sinus-Pak). Each disc was then dip coated in a diluted solution of Ti3C2 MXene (Murata) (20 mg / ml). The expanded discs were then air dried. Subsequently an Ag / AgCl button snap connector was then adhered to one side of the pillar with conductive silver epoxy. The epoxy was cured in an oven at 80°C.

[0087] Scanning electron microscopy

[0088] Scanning Electron Microscope (SEM) images were collected under high vacuum (5×10^−5 Torr) using the FEI Quanta 600 FEG Mark II Environmental SEM using back scattering electrons signals and Energy Dispersive X-ray Spectrometry (EDS) detector installed for elemental analysis. The Ti3C2TxMXene coated PVA pillars were imaged with a working distance of 9.3 mm, overall electron beam acceleration voltage of 10 kV and a spot size of 6, the raw PVA pillars had a working distance of 8.9 mm. SEM images of the MXene pillars were acquired with a 30 us dwell time integrating 4 frames, while the PVA pillars were integrated with 16 frames to prevent drifting.

[0089] Raman spectroscopy analysis

[0090] Raman spectroscopy was performed using a Horiba Raman and AFM system with a 785 nm excitation laser (50x objective, 25% ND filter). Raman spectra of Ti3C2TxMXene coated PVA were acquired for 30 s per scan and averaged across 5 - 20 - 4855-6384-0993.125-10873 / 103241.007486 scans, while Raman spectra of uncoated PVA were acquired for 20 s per scan and averaged across 5 scans.

[0091] Headset fabrication

[0092] The core of the EGG headset is made from elastic material providing flexibility and comfort while maintaining electrode placement. Using the frontal and temporal regions of an EEG 10 / 20 template, 8mm diameter holes are cut out for eight electrodes- Fp1, F7, T3, T5, Fp2, F8, T4, and T6. To ensure versatility and a secure fit across varying head sizes, a plastic clasp mechanism is attached via sewing onto one end of the headband, complemented by an ample allowance of elastic material flanking the final electrode, aligning with template guidelines. Snap-in holders for the Shimmer electrode leads were custom designed using SolidWorks and 3D printed in Formlabs Durable Resin on a Form3 SLA 3D printer. Durable resin was chosen for the thin parts to allow a snug fit of the electrode leads without them breaking from elongation forces. The MXtrode seamlessly snaps into the lead mounted within the holder, fortifying its attachment to the headband, while smaller holes in the 3D printed holder facilitate hand-sewn attachment to the headband. Reference and ground connections were established via a disposable adhesive gel electrode placed on either mastoid bone. Soldered connections link the Shimmer electrode leads to connecting wires, which are neatly bundled and secured using shrink wrap. The wires ultimately plug into the touchpoint box, which is connected to the Ripple processor for recording.

[0093] Mechanical testing

[0094] An Instron was used to compress pillars by 80% of their height using a 15N load cell for up to 50 cycles. The resulting force and extension were then measured. After each compression the interface impedance was measured using electrochemical testing methods stated below.

[0095] Electrochemical testing - 21 - 4855-6384-0993.125-10873 / 103241.007486

[0096] EIS of the MXene electrode pillar was performed with a Gamry Reference 600 potentiostat in room temperature on the surface of an agarose skin phantom (0.6% w / w agarose and 0.3% w / w NaCl) using a three-electrode configuration. Two Ag / AgCl (20mm disk or 3mm cup) electrodes were used as a reference electrode and counter electrode. An impedance spectrum was constructed using measures obtained at frequency values ranging from 1 Hz to 1 MHz with a 10 mVrmsinput AC voltage.

[0097] Limited montage recordings

[0098] Two different experiments were run to demonstrate the use of our limited montage headcap for EEG recordings. All EEG recording experiments were approved by the Institutional Review Board (IRB) of the University of Pennsylvania (protocol no. 832421). The purpose of the first study was to benchmark MXene based dry electrodes against clinical gelled cup electrodes.

[0099] Patients that were already scheduled to receive a routine outpatient EEG were recruited to take part in this study prior to their clinical recording (N = 5 participants). The Natus EEG amplifier system and software were used to record EEG (sampling rate = 250 Hz). All data was de-identified and stored on ieeg.org. In the second study EEG was record from healthy human subjects affiliated with the University of Pennsylvania, while walking to evaluate the feasibility of EEG recording in the dynamic environments (N = 5 subjects). The Ripple grapevine amplifier and Trellis software were used to collect data (sampling rate = 30 kHz). Informed consent was obtained from all participants. For both studies, electrodes were snapped into the limited montage 8- channels band ahead of the recording session.

[0100] The band with electrodes was placed on the patient with the front tab centered on the nasion bone. Two 3 mm Ag / AgCl Natus gelled cup electrodes were placed on the midline for reference and ground for clinical recordings. For our ambulatory, dynamic recording tests, two Ag / AgCl 20mm disk electrodes were used on the mastoid as reference and ground. The skin under each dry electrode contact was wiped with an 70% alcohol preparation pad and followed by the addition of a drop of approximately 1 mL of 1X phosphate buffered saline. For clinical recordings participants were asked to open and close their eyes for 2 to 3 minutes durations during the recording.

[0101] The dry electrode cap was removed at the end of the session and clinical Ag / AgCl Natus gelled electrodes were placed on the full scalp in addition the locations - 22 - 4855-6384-0993.125-10873 / 103241.007486 used for MXene recording for the routine EEG, in which the same eyes open and close tasks were completed. For dynamic recordings participants wore the limited montage recording band and were asked to sit, stand, and walk with their eyes closed for one minute each.

[0102] Full head recordings

[0103] To evaluate electrode performance over the full scalp, dry EEG recording was performed on healthy human subjects affiliated with Drexel University. This EEG recording experiment was approved by the IRB of Drexel University (protocol no.1904007140). Informed consent was obtained from all participants (N =5). MXene pillar electrodes were placed in the full head cap and the cap was then placed on participants, lining up the tab on the front of the cap with the naison bone for alignment. The skin under each dry electrode contact was wiped with an 70% alcohol preparation pad and followed by the addition of a drop of approximately 1 mL of 1X phosphate buffered saline.

[0104] Three gelled, passive, Ag / AgCl cup electrodes (Technomed Disposable EEG Cup Electrodes) were also included for comparison. They were placed at Fpz, C3, and Oz. Additional Technomed gelled Ag / AgCl electrodes were used for ground and reference, placed at the right and left mastoid, respectively. All MXtrodes, gelled Ag / AgCl electrodes, ground, and reference were simultaneously connected to a Bittium NeurOne Tesla EEG system (Bittium Corporation, Finland) via jackbox. We recorded EEG in a shielded room using a passive Bittium NeurOne Tesla EEG system at a sampling rate of 5kHz using the Tesla hardware filters.

[0105] As part of a larger cognitive experiment, we recorded EEG while participants performed a two-minute resting-state block with their eyes open. In this block, participants sat quietly and looked at a fixation cross on a computer screen. We also recorded EEG while the participants stared at the same fixation cross while tapping their right pointer finger for two minutes and while holding still but imagining they were tapping their right pointer finger for two minutes.

[0106] Additionally, we recorded EEG during a two-minute block of a 20Hz steady-state visually evoked potential (SSVEP) paradigm. We used PsychoPy® (Peirce et al., 2019) to display a basic luminance based SSVEP paradigm where a square in the center of the computer screen flickered between black and white at 20Hz on a grey - 23 - 4855-6384-0993.125-10873 / 103241.007486 background (Arizpe, 2018). Due to the computer's system load, the actual flickering rate presented to the participants varied between 20.3Hz and 20.9Hz. The flickering rate was consistent within each participant, and these small fluctuations did not impact the analysis other than resulting in slight differences in the exact peak of the SSVEP response in the EEG spectrum.

[0107] Safety concerns arise when traditional EEG electrodes are used in conjunction with TMS due to the interaction between TMS-generated magnetic fields and the conductive materials in these electrodes. Specifically, adverse effects such as electrode displacement, heating, and secondary currents can occur and compromise patient safety and EEG recording quality. Therefore, it is useful to establish the safety profiles of electrodes under TMS conditions and ensure their compatibility and reliability for use in TMS-EEG applications. Here, we investigated the TMS safety of dry Ti3C2Txelectrodes and benchmarked against commercial TMS-compatible split-ring type electrodes commonly used in TMS-EEG (Ag / AgCl B18 model from EasyCap), (FIG.17A,B). In this study, we adopted two experimental setups. For displacement testing, a dry Ti3C2Txelectrode and an Ag / AgCl electrode were suspended in air side-by-side, 1 mm from the TMS coil (FIG.17A). A Canon EOS M50 high-definition digital camera was positioned parallel to the electrodes to capture and then quantify displacement. The electrodes were subjected to two different TMS protocols: single pulses delivered at 60%, 70%, 80%, and 90% machine output (MO), and 50 Hz theta burst stimulation at 45% MO for 10 seconds. No measurable movement was detected in both dry Ti3C2Txelectrodes and Ag / AgCl electrodes under any of the investigated TMS protocols (FIG.17C).

[0108] For temperature and induced voltage and charge testing, two adjacent Ti3C2Txelectrodes and one Ag / AgCl electrode were mounted on a conductive 0.6% agarose phantom, and the temperature at the electrode surface was monitored with a fiber optic probe placed between the electrodes and the agarose phantom. Electrode voltage was continuously measured during 10 Hz TMS stimulation at 80% MO and a 50 Hz theta burst sequence at 45% MO, both delivered over 30-second intervals. The maximum temperature increase during both TMS protocols on the dry Ti3C2TxMXene electrode was 0.08 ± 0.02°C (initial temperature: 18.26 ± 0.67°C, final temperature: 18.34 ± 0.65°C), well below the 6°C safety threshold recommended for devices in contact with the skin during neurostimulation (FIG.17D). The Ag / AgCl electrodes also showed no temperature - 24 - 4855-6384-0993.125-10873 / 103241.007486 changes (initial temperature: 17.85 ± 0.69°C, final temperature: 17.89 ± 0.69 °C) (FIG. 17E). As for the induced voltage from TMS, the 10 Hz TMS at 80% output and the 50 Hz theta burst TMS at 45% output produced 12.63 ± 0.14 V and 6.76 ± 0.06 V, across adjacent Ti3C2Txelectrodes, respectively (peak-to-peak values; FIG.17E,F). The corresponding charge densities on the electrodes, calculated with eq.1, were 2.87 ± 0.05 μC / cm² (10 Hz at 80% output) and 1.35 ± 0.01 μC / cm² (50 Hz theta burst at 45% output; FIG.17G), which are in both cases significantly below the 30 μC / cm² safety limit to prevent tissue damage. Excessive charge densities can cause electrolytic tissue damage. Minimal heating of MXene electrodes also presents a potential advantage for blinding in neuromodulation studies. In some studies, sham conditions are designed to minimize or eliminate heating, which can otherwise serve as a sensory cue that compromises subject blinding. By demonstrating that MXene electrodes produce very low heating, participants are less likely to detect differences in thermal sensation between active and sham stimulation, improving the robustness of blinded study designs.

[0109] Consistent and comfortable placement of the electrodes on the scalp is key to ensuring repeatability, reliability, and quality of EEG recordings. Ag / AgCl gelled electrodes are widely used for full scalp EEG and are useful in ensuring proper adhesion between the electrodes and the scalp due to the presence of gel, while minimizing subject- to-subject scalp variability and impedance. Due to the lack of such gels, consistent and comfortable placement of dry EEG in addition to acquiring adequate signal can involve some care, especially when attempting to record from the full scalp. Here, we sought to validate and benchmark the 21-channel dry Ti3C2TxEEG headset (i.e., 10-20 system) against commercial Ag / AgCl gelled electrodes during common tasks performed in cognitive research and BCI paradigms to ensure we could record EEG across the full scalp. In these studies, we asked participants (n=5) to wear the 10-20 dry Ti3C2Txheadcap placed using a minimal skin preparation protocol . Then, we placed 3 additional Ag / AgCl cup electrodes (3 mm diameter) adjacent to 3 dry electrodes for direct comparison of signals across scalp sites with varying levels of hair density: Frontal (Fp1), Motor (C3), and Occipital (O2) (FIG.18A). Reference and ground Ag / AgCl electrodes were placed on the mastoid. Then, we checked the impedance to ensure that all electrodes were < 100 kΩ and showed a stabilized baseline signal on the Bittium neurOne amplifier. We collected 2 minutes of resting state EEG, then asked participants to observe a screen with a 20 Hz - 25 - 4855-6384-0993.125-10873 / 103241.007486 flashing stimulus source for 2 minutes (FIG.18B). These flashing visual stimuli are expected to elicit a 20 Hz steady-state visual evoked potential (SSVEP) response, which is accepted for BCIs.

[0110] EEG collected on dry Ti3C2Txelectrodes was highly comparable to adjacent Ag / AgCl sites, as also indicated by Pearson correlations >0.8 throughout the whole recording session (i.e., resting state + SSVEP task, Fp1: 0.895 ± 0.059, C3: 0.929 ± 0.047, O2: 0.989 ± 0.011; n=5 electrode pairs; FIG.18C,D). In the SSVEP task, across all participants, we observed the expected increase in the power spectral density (PSD) and SNR of the EEG collected on dry Ti3C2Txelectrodes centered at the frequency of the visual stimulation (i.e., 20 Hz, FIG.18E). Specifically, we found that the increase in SNR at 20 Hz compared to resting states of electrodes in the region of interest (P3, P4, Pz, O1, O2) was significant across all participants (2 sample t-test, 5% significance level, p = 0.01 ± 0.01). This increase in the 20 Hz response is also observed on the most proximal gelled Ag / AgCl electrode placed in the occipital region. Topographical maps of the 20 Hz power distribution on the scalp built from the full-scalp dry EEG recordings (FIG.18F) show that the 20 Hz activity was spatially localized on the occipital electrodes, which are the most proximal to the visual cortex. Overall, these results demonstrate the ability to record full- scalp EEG with a 10-20 dry Ti3C2Txheadset designed to optimize scalp contact and user comfort. Furthermore, the full-scalp dry Ti3C2Txheadsets can collect EEG signals of the same quality and reliability of state-of-the-art commercial Ag / AgCl electrodes and capture relevant EEG features for cognitive and BCI research applications.

[0111] Aspects

[0112] The following Aspects are illustrative only and do not limit the scope of the present disclosure or the appended claims. Any part or parts of any one or more Aspects can be combined with any part or parts of any one or more other Aspects.

[0113] Aspect 1. A conductive sensor lead, comprising: a resilient permeable substrate material; the resilient permeable substrate material comprising a first surface and a second surface, the second surface being configured for contact with a subject, and a solid electrically conductive material disposed within the resilient permeable substrate material so as provide a conductive path between the first surface and the second surface; and a conductive contact associated with the first surface. - 26 - 4855-6384-0993.125-10873 / 103241.007486

[0114] The resilient permeable substrate material can be in a cylinder shape. This is not, however, a requirement, as the resilient permeable substrate material can be in a polygonal, spherical, conical, or other shape, depending on the user’s and application needs. The conductive sensor lead can be in electrical communication with a wire or other connector; such a connector can, for example, connect the conductive sensor lead to a source of voltage and / or current. As shown in FIG.1A, a sensor lead can comprise the resilient permeable material having solid electrically conductive material disposed within, and a connector. Such a connector can, for example be adhered or otherwise fixed to the resilient material. In some embodiments, the connector is engaged with the resilient material so as to remain in place without the user of an adhesive. For the resilient material can include a feature that engages with at least a portion of the connector such that the connector is retained in place. This can be, for example where the resilient material includes a slot, hole, or other feature that engages with a part – such as a tab, peg, or other feature – of the connector so as to secure the resilient material and the connector together.

[0115] When the resilient material is connected to an electrical lead – such as a wire or cable – additional material can be present between the resilient material and the lead. For example, in order for current to flow from the lead to the resilient material, the current may have to first pass through a connector and, when present, an adhesive. In some embodiments, the resilient material of the sensor lead is not direct physical contact with the electrical lead associated with that sensor lead.

[0116] Aspect 2. The sensor lead of Aspect 1, wherein the resilient permeable substrate material is characterized as an absorbent material, the resilient permeable substrate material optionally comprising a sponge. Without being bound to any particular embodiment, a sponge is considered particularly suitable.

[0117] Aspect 3. The sensor lead of any one of Aspects 1-2, wherein the resilient permeable substrate material comprises a polymer.

[0118] Aspect 4. The sensor lead of Aspect 3, wherein the polymer comprises any one or more of polyvinyl alcohol (PVA), polyurethane, polylactic acid (PLA), cellulose, polyethylene, and silicone foam. The foregoing is not an exhaustive listing, as other polymers and absorbent materials can be used with the disclosed technology.

[0119] Aspect 5. The sensor lead of any one of Aspects 1-4, wherein the electrically conductive material comprises MXenes or other conductive materials. - 27 - 4855-6384-0993.125-10873 / 103241.007486

[0120] Aspect 6. The sensor lead of any one of Aspects 1-5, wherein the conductive contact comprises any one or more of a conductive adhesive, a button snap, or a connector. A variety of connectors can be used with the disclosed technology, and the optimal connector for a given application will be determined by the user. The conductive adhesive, a button snap, or a connector can in turn be in electrical communication with a wire or cable, which wire or cable can place the sensor lead into electrical communication with a source of voltage and / or current.

[0121] Aspect 7. The sensor lead of any one of Aspects 1-6, wherein the conductive contact is adhered to the first surface.

[0122] Aspect 8. The sensor lead of any one of Aspects 1-7, wherein the sensor lead is comprised in a fixture, the fixture optionally being conformable to a subject, and the fixture optionally comprising an electrode configured to engage with a sensor lead.

[0123] Aspect 9. The sensor lead of Aspect 8, wherein the fixture comprises any one or more of a band, a pad, a mesh, a headset, and a cap. The disclosed sensor leads can be comprised in, for example, an EEG system or part thereof. The disclosed sensor leads can be arranged in, for example, a line, a pattern, or individually. The arrangement of the leads can be according to the user’s needs, application type, or according to other usability and ergonomic considerations.

[0124] Aspect 10. A method, comprising collecting a signal from a sensor lead according to any one of Aspects 1-9.

[0125] Aspect 11. The method of Aspect 10, wherein the signal is a neurological signal.

[0126] Aspect 12. A system, comprising: a fixture comprising a plurality of sensor leads, a sensor lead comprising (i) a resilient permeable substrate material having first and second surfaces, and (ii) a solid electrically conductive material placed within the resilient permeable substrate material so as to provide a conductive path between the first and second surfaces of the resilient permeable substrate, and the sensor lead configured for electronic communication with a receiver configured to collect a signal from the sensor lead.

[0127] A sensor lead can, for example, be a sensor lead according to any one of Aspects 1-9. Sensor leads comprised in the fixture can be individually addressable. - 28 - 4855-6384-0993.125-10873 / 103241.007486

[0128] Aspect 13. The system of Aspect 12, wherein the resilient permeable substrate material is characterized as a sponge.

[0129] Aspect 14. The system of any one of Aspects 12-13, wherein the electrically conductive material comprises a MXene. It should be understood that MXenes are an example electrically conductive material. Other example electrically conductive materials include graphite, carbon black, carbon nanotubes, a metal, and the like. The conductive material can be solid, dry, or both solid and dry. Likewise, the resilient permeable substrate material can be solid, dry, or both solid and dry. The disclosed leads can be used in a dry state.

[0130] Aspect 15. The system of any one of Aspects 12-14, wherein the fixture comprises any one or more of a band, a pad, a mesh, a headset, and a cap.

[0131] Aspect 16. The system of any one of Aspects 12-15, wherein the system further comprises a receiver in electronic communication with the receiver configured to collect a signal from the sensor lead.

[0132] Aspect 17. The system of any one of Aspects 12-16, wherein the system is characterized as wearable.

[0133] Aspect 18. The system of any one of Aspects 12-17, wherein the system is characterized as an EEG, an electromyography (EMG), a functional electrical stimulation (FES) system, a transcutaneous muscle (TEMS) system, a transcutaneous nerve stimulation (TENS) system, and other wearable sensor and stimulation systems. The system can be a portable system, but this is not a requirement, as the disclosed technology can be used in a stationary system.

[0134] Aspect 19. A method, comprising collecting a signal from a system according to any one of Aspects 12-18. Such signal collection can be, for example, performed in connection with any one of more of an EEG study, a FES study, a TEMS study, and a TENS study. The disclosed technology is considered particularly suitable for EEG studies.

[0135] As shown herein, the disclosed technology can be used to perform a study where saline – rather than a conductive gel or paste – is used at the interface between the subject and the sensor lead, for example as described at FIG.10. This is a particular advantage of the disclosed technology, as the tapes, adhesives, and conductive pastes associated with traditional electrodes need not necessarily be used with the - 29 - 4855-6384-0993.125-10873 / 103241.007486 disclosed technology. The disclosed sensor leads can, however, be used “dry” when performing a study and can be applied directly to a subject.

[0136] Aspect 20. The method of Aspect 19, wherein the signal is any one or more of a biological signal and a neurological signal. The disclosed technology can be used, for example, to develop a 2-D or even a 3-D map of signals collected from sensor leads associated with a subject, as shown in FIG.18F. - 30 - 4855-6384-0993.1

Claims

25-10873 / 103241.007486 What is Claimed:

1. A conductive sensor lead, comprising: a resilient permeable substrate material; the resilient permeable substrate material comprising a first surface and a second surface, the second surface being configured for contact with a subject, and a solid electrically conductive material disposed within the resilient permeable substrate material so as provide a conductive path between the first surface and the second surface; and a conductive contact associated with the first surface.

2. The sensor lead of claim 1, wherein the resilient permeable substrate material is characterized as an absorbent material, the resilient permeable substrate material optionally comprising a sponge.

3. The sensor lead of any one of claims 1-2, wherein the resilient permeable substrate material comprises a polymer.

4. The sensor lead of claim 3, wherein the polymer comprises any one or more of polyvinyl alcohol (PVA), polyurethane, polylactic acid (PLA), cellulose, polyethylene, and silicone foam.

5. The sensor lead of any one of claims 1-2, wherein the solid electrically conductive material comprises a MXene.

6. The sensor lead of any one of claims 1-2, wherein the conductive contact comprises any one or more of a conductive adhesive, a button snap, or a connector.

7. The sensor lead of any one of claims 1-2, wherein the conductive contact is adhered to the first surface. - 31 - 4855-6384-0993.125-10873 / 103241.007486 8. The sensor lead of any one of claims 1-2, wherein the sensor lead is comprised in a fixture, the fixture optionally being conformable to a subject, and the fixture optionally comprising an electrode configured to engage with a sensor lead.

9. The sensor lead of claim 8, wherein the fixture comprises any one or more of a band, a mesh, a headset, a pad, and a cap.

10. A method, comprising collecting a signal from a sensor lead according to any one of claims 1-2.

11. The method of claim 10, wherein the signal is a neurological signal.

12. A system, comprising: a fixture comprising a plurality of sensor leads, a sensor lead comprising (i) a resilient permeable substrate material having first and second surfaces, and (ii) a solid electrically conductive material placed within the resilient permeable substrate material so as to provide a conductive path between the first and second surfaces of the resilient permeable substrate material, and the sensor lead configured for electronic communication with a receiver configured to collect a signal from the sensor lead.

13. The system of claim 12, wherein the resilient permeable substrate material is characterized as a sponge.

14. The system of any one of claims 12-13, wherein the solid electrically conductive material comprises a MXene.

15. The system of any one of claims 12-13, wherein the fixture comprises any one or more of a band, a pad, a mesh, a headset, and a cap.

16. The system of any one of claims 12-13, wherein the system further comprises a receiver in electronic communication with the receiver configured to collect a signal from the sensor lead. - 32 - 4855-6384-0993.125-10873 / 103241.007486 17. The system of any one of claims 12-13, wherein the system is characterized as wearable.

18. The system of any one of claims 12-13, wherein the system is characterized as any one or more of an EEG system, an electromyography (EMG system), a functional electrical stimulation (FES) system, a transcutaneous muscle (TEMS) system, a transcutaneous nerve stimulation (TENS) system, and another wearable sensor and stimulation system.

19. A method, comprising collecting a signal from a system according to any one of claims 12-13.

20. The method of claim 19, wherein the signal is any one or more of a biological signal and a neurological signal. - 33 - 4855-6384-0993.1

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