MRI and CT Compatible Asymmetric Bilayer Hydrogel Electrodes for EEG-Based Brain Activity Monitoring

MRI and CT Compatible Asymmetric Bilayer Hydrogel Electrodes for EEG-Based Brain Activity Monitoring | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article MRI and CT Compatible Asymmetric Bilayer Hydrogel Electrodes for EEG-Based Brain Activity Monitoring Qifeng Lu, Guoqiang Ren Ren, Mingxuan Zhang, Liping Zhuang, Lianhui Li, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4657809/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract The exploration of the multi-dimensional brain activity with high temporal resolution and spatial resolution is of great significance in the diagnosis of neurological disease and the study of brain science. Although the integration of EEG with magnetic resonance imaging (MRI) and computed tomography (CT) provides a potential solution to achieve the brain-functional image with high spatiotemporal resolution, the critical issues of interface stability and magnetic compatibility remain challenges. Therefore, in this research, we proposed a conductive hydrogel EEG electrode with an asymmetrical bilayer structure, which shows the potential to overcome the challenges. Benefited from the bilayer structure with different moduli, the hydrogel electrode exhibits high biological and mechanical compatibility with the heterogeneous brain-electrode interface. As a result, the impedance can be reduced compared with conventional metal electrodes. In addition, the hydrogel-based ionic conductive electrodes, which are free from metal conductors, are compatible with MRI and CT. Therefore, it can obtain high spatiotemporal resolution multi-dimensional brain information in clinical settings. The research outcome provides a new approach for establishing a platform for early diagnosis of brain diseases and the study of brain science. Physical sciences/Materials science Physical sciences/Engineering Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction According to the World Health Organization (WHO), approximately one-third of the global population experiences neurological disorders, which are the leading causes of health loss and disability worldwide 1 – 3 . The diagnosis of neurological disorders is realized by the acquisition and analysis of electroencephalogram (EEG) signals due to its non-invasive property as shown in Fig. 1 A. This approach is pivotal for managing neurological conditions and ensuring high-quality care, treatment, and rehabilitation services for patients 4 – 6 . However, EEG signals, characterized by frequencies from 0.5 to 100 Hz and amplitudes ranging from 1 to 200 µV, are prone to attenuation and distortion due to impedance mismatch when transmitted through subcutaneous tissues to the brain interface 7 , 8 . Moreover, human body movement generates additional interference to the EEG signals 9 – 11 . Consequently, the development of EEG electrodes capable of long-term signal collection is crucial for precision medical testing in neural diseases 12 , 13 . Ionic conductive hydrogel, a soft material renowned for its excellent moisture retention and unique ion transport mechanism, is ideal for flexible devices and systems with high stretchability, conformal adhesion, noise filtration, and compatibility 14 – 22 . Consequently, a number of studies have been conducted on hydrogel electrodes 23 – 27 . Seung Hwan Ko's team utilized PEDOT: PSS as a conductive filler to create high-stability conductive hydrogels that adhere to various substrates through laser-induced phase separation and interface structures. This method enables the selective transformation of conducting polymers into conductive hydrogels with wet conductivities of 101.4 S/cm and patterning with a spatial resolution as fine as 5 µm 28 . Yan and Zhang explored the development of a highly conductive, viscoelastic, and biocompatible hydrogel, capable of establishing an efficient and stable interface between human tissue and electrodes, yielding high-quality EEG signals via a non-invasive approach 29 . In collaboration with Suo, Wang introduced an implantable subdural cortical electrode with high transparency and low modulus, compatible with optogenetic equipment for multidimensional brain information detection in animal models 30 . However, the single-mode EEG signal suffers from low spatial resolution and has an impact on the feature identification accuracy. While CT and MRI offer higher spatial resolution for brain structural and functional signals, their strong magnetic fields significantly interference with EEG sensors 31 – 35 . Consequently, The EEG electrodes, which is able to record EEG with CT and MRI images simultaneously has yet to be reported. In this research, an asymmetrical bilayer hydrogel EEG electrode was proposed, featuring a lower modulus layer (HBE-1) and a higher modulus upper layer (HBE-2) in its structure as shown in Fig. 1 B. The bilayer design endows the hydrogel with high conductivity, flexibility, and biocompatibility. Therefore, the high-quality EEG signals can be collected. In addition, benefited from metal-free property, the ionic conductive hydrogel is compatible with strong magnetic fields, which ensures its suitability in operation of CT and MRI environments. As a demonstration, the integration of EEG with CT/MRI was achieved for the EEG signal and brain structural image recording as shown in Fig. 1 C. This method facilitates high temporal and spatial resolution brain disease examinations. The research outcomes offer a novel approach for multi-dimensional brain information monitoring and the diagnosis of brain diseases. Result and Discussions Mechanical properties of the hydrogel Figure 2 presents the mechanical performance of the hydrogel under different strain and temperature conditions. Figure 2 A-C demonstrate that HBE-1 exhibits higher adhesion force within a lower strain range and has a low Young’s modulus of 0.12 ~ 0.15 MPa. In contrast, HBE-2 shows higher flexibility and toughness within a higher strain range, with a high Young’s modulus of 0.35 ~ 0.38 MPa. The bilayer structure of HBE has the advantages of both layers with the Young’s modulus between that of HBE-1 and HBE-2 (0.22 ~ 0.28 MPa). The storage modulus of HBE-1 in Fig. 2 D indicates its high flexibility under dynamic conditions within the 0.1 ~ 10Hz tensile vibration frequency. HBE-2 exhibits the highest storage modulus as well as a higher loss modulus, which indicates its higher rigidity and energy dissipation under dynamic conditions. The storage modulus and loss modulus of HBE are between those of HBE-1 and HBE-2. Figure 2 E and Fig. 2 F illustrate that HBE-2 shows the smallest variation in complex modulus under different temperatures. The results demonstrate its good stability under various temperature conditions. The static and dynamic mechanical performance of the hydrogel can provide evidence for the selection of appropriate hydrogel layers based on the requirements. The HBE has good resistance to water loss within 48 hours (Fig. S1 , Supporting Information). For applications with higher demands for comprehensive performance in clinical applications, the bilayer structure of HBE can be adopted to ensure the stable recording of signals. Adhesion properties of the hydrogel The adhesion property of the hydrogel electrode is crucial for stable and reliable EEG signal monitoring, which is the fundamental requirement for accurate data collection and comfortable long-term wear. Therefore, the adhesion model of the hydrogel electrode on the surface of the skin was established by COMSOL. The adhesion process of the electrode on the skin surface and the distribution of adhesion strength were investigated and shown in Fig. 3 A-F. In detail, Fig. 3 A and 3 D show the deformation of the hydrogel on the skin under tension, which demonstrates that the hydrogel undergoes maximum tensile deformation at the center of the skin strain according to simulation results. Figure 3 B and 3 E illustrate the stress distribution and adhesion strength changes resulting from the stretch of the hydrogel. The results indicate that no significant impact was observed on the contact area with the skin surface. Figure 3 C and Fig. 3 F demonstrate the effect of the tensile deformation of the hydrogel. Simulation results show that the hydrogel exhibits uniform adhesion stress distribution on the skin surface which enables the stable attachment to biological tissue without significant stress during stretching. A 90-degree peel test was conducted using the Instron universal material testing machine at a loading rate of 5mm/min. The peel adhesion strength of the hydrogel gradually increases within the displacement range of 0 ~ 60 mm and reaches a maximum value of approximately 45 kPa as shown in Fig. 3 G. The peel test results indicate that the hydrogel exhibits high peel adhesion strength and maintains stable adhesion performance within a large displacement range. In addition, the hydrogel was adhered to the wrist and fingers of the subjects to investigate the adhesion property during the bending and stretching states as shown in Fig. 3 H. The findings demonstrate that the hydrogel can stably adhere to the wrists and fingers of individuals during movement, indicating its potential for long-term wearable and flexible systems. Electrical properties of hydrogel-based EEG electrodes The electrical impedance of the hydrogel-based EEG electrodes is also a crucial parameter in signal fidelity and reliability, which is important for neurophysiological studies. Figure 4 A shows the electrical impedance spectra (EIS) of Au, HBE, HBE-1, and HBE-2 electrodes. The impedance of the Au electrode is significantly higher than that of the HBE electrode, indicating the better ion conductivity of the HBE electrode. Figure 4 B illustrates the phase angle variation with frequency. The phase angle of the HBE electrode approaches 90 degrees in the low-frequency range, suggesting stronger capacitive behavior. Figure 4 C displays the impedance variation with frequency. The impedance of the HBE electrode is significantly lower than that of the Au electrode, reaching the lowest impedance value after 1 hour. In Fig. 4 D, the conductivity remains steady at approximately 0.7–0.9 S/m with no significant decrease in the conductivity observed within the following one hour. Figure 4 E presents the cyclic voltammetry curves of the HBE, HBE-1, and HBE-2 electrodes. The current response of the HBE electrode is significantly higher than that of the single-layer hydrogel electrode, HBE-2, indicating its superior comprehensive conductive performance. The cyclic voltammetry curves of the HBE electrode at different tensile strains of 0%, 20%, and 50% were performed to test the reliability of the electrode during movement. As depicted in Fig. 4 F, no significant change was observed. Figure 4 G demonstrates the long-term stability of the HBE electrode, showing that the electrode can work stably for more than 12 hours. Figure 4 H-I show the input and output voltage waveforms at different frequencies, indicating that the HBE electrodes can effectively respond to the input signals up to 10 kHz. Biocompatibility of the EEG electrodes Biocompatibility is a crucial factor for hydrogel electrodes to be used in biological systems without adverse effects. Therefore, cytocompatibility and hemocompatibility were investigated in our research. The cytocompatibility of the CCK8 cell viability assay is shown in Fig. 5 A. Both the PVA/PEG and HBE materials sustained cell viability exceeding 90% over 1, 2, and 3 days, which is close to the PBS control group. This result indicates the minimal cytotoxicity towards L929 fibroblasts. In Fig. 5 B, the hemolysis rate of the HBE material is notably lower than that of Triton X-100 (positive control), which indicates that no significant difference between the hydrogel and the PBS control group. Figure 5 C and Fig. 5 D present the results of the Live/Dead immunofluorescence staining. The HaCaT cells and human dermal fibroblasts within the PVA/PEG and HBE material groups exhibit vigorous growth, elevated cell density, and uncompromised morphology over 1, 2, and 3 days, without any appreciable discrepancies from the control group. This result confirms the exceptional cytocompatibility of the material. The hematoxylin and eosin (H&E) and Masson staining shown in Fig. 5 E reveal that the skin tissue remained unperturbed after the application of the HBE to the rat dorsum for 3 and 12 hours. No discernible influx of inflammatory cells or tissue perturbation was observed, indicating that the HBE material does not provoke skin irritation. EEG signals recorded by hydrogel-based electrodes After investigating the basic electrical and mechanical properties of the hydrogel, we conducted the EEG signal monitoring with the hydrogel-based electrodes and analyzed the EEG signals and brain topography. Figure 6 A depicts the EEG signal recording in a relaxed sitting state, deep breathing in a sitting position, and exposure to a flashing light. From the energy spectrum, correlation distribution, and amplitude from EEG signals and brain topography in Fig. 6 B and Fig. 6 C, the EEG signals appear relatively stable, with minimal potential fluctuations across all channels, which indicates low brain activity of the subjects in the relaxed state. Representative EEG signals in 295 to 299 seconds with HBE electrodes (Fig. S2 , Supporting Information). The analysis of brain topography and energy spectrum confirms that the signals concentrated in the 0.5-4.0 Hz (Delta waves) and 4.0–8.0 Hz (Theta waves) frequency ranges are mainly associated with relaxation. During deep breathing, noticeable rhythmic changes in the EEG waveforms are observed, which is consistent with the respiratory frequency. The energy spectrum in the 4.0–8.0 Hz (Theta waves) and 8.0–13.0 Hz (Alpha waves) frequency bands reflect the significant impact of deep breathing on brain electrical activity. In addition, there is a slight coherence increase than that in the relaxed state, which can be attributed to the enhanced brain activity. Under flashing light with a frequency of 10 Hz, a strong synchronized response is observed in the EEG waveforms. Significant enhancement in brain electrical activity appears in the 8.0–13.0 Hz (Alpha waves) and 13.0–30.0 Hz (Beta waves), accompanied by a noteworthy increase in coherence in the Alpha and Beta bands. The amplitudes are significantly enhanced due to the substantial brain electrical response to flashing light frequency. When the flashing frequency increases to 30 Hz, the EEG waveforms exhibit pronounced synchronized patterns with significant enhancement in brain activity observed in the 13.0–30.0 Hz (Beta waves) frequency band. The amplitudes also significantly increase, indicating a notable impact of the flashing frequency of the light on high-frequency brain electrical activity. The analysis of EEG signals with the brain topography shows that the Delta and Theta waves are concentrated in the forehead, while Alpha and Beta waves are lower and evenly distributed across the scalp, signifying uniform electrical activity in these bands across the entire head. High coherence in the 0.5-4.0 Hz frequency range, especially in the forehead, indicates strong synchronized activity in the low-frequency range in the forehead. Low coherence in the 4.0–30.0 Hz frequency range suggests poor synchronization of electrical activity across different regions. The high amplitudes distributed in the middle and anterior regions of the head indicate greater electrical activity strength in these areas. The energy spectrum, coherence distribution, and amplitude of brain electrical activity under different states and stimuli in the research show potential for providing a comprehensive foundation for clinical examinations, diagnosis, and treatment recommendations for brain disease. Compatibility of hydrogel-based EEG electrodes in CT and MRI environment Finally, the compatibility of the EEG hydrogel electrode with MRI and CT was conducted to demonstrate its potential application in clinical diagnosis. The CT images Fig. 7A1 and Fig. 7A2 of display the skull and brain structures. In contrast to the metal electrodes, no interference with the imaging is observed in the presence of the hydrogel electrodes. Figure 7B1 and B2 present the brain tissue structures with hydrogel electrodes, and almost no impact on the quality of the MRI images, such as magnetic resonance artifacts, was observed. The result indicates that the hydrogel electrodes can be used in both CT and MRI environments without the issues of artifacts as in traditional metal electrodes. Conclusion The hydrogel, a soft and biocompatible material, has a great potential in flexible and wearable systems for long-term monitoring of biological signals with comfort and no skin irritation. In this study, an asymmetric bilayer hydrogel was designed and synthesized for EEG electrodes. The top layer, characterized by a high modulus, ensures high conductivity, whereas the bottom layer, with a low modulus, improves wearing comfort and skin conformality. This bilayer design not only enhances interface contact but also maintains structural stability. High-quality EEG signals were successfully recorded in various states, including relaxation, deep breathing, and flash stimulation. In addition, the metal-free nature of the hydrogel electrodes allows compatibility with CT and MRI without generating artifacts. Consequently, the proposed hydrogel-based electrodes provide substantial benefits for monitoring complex brain activities and shows a potential in simultaneous recording of multi-dimensional brain activity. The research findings lay a foundation for the comprehensive study of brain diseases and brain science. Materials and methods Materials Polyvinyl alcohol (PVA-117, Mw ~ 145, 000), Polyethylene glycol (Average Mn 4, 000), and NaCl (Medical grade) were sourced from Shanghai Aladdin Industrial Corporation Co. Ltd. All other materials, unless specified, were commercially available and used as received. The deionized water utilized in the experiments consistently met Milli-Q grade standards with a resistivity of 18.2 MΩ. Synthesis of HBE and PVA/PEG Hydrogel 20 g PVA was dissolved in 80 mL of a 5% NaCl solution and the solution was stirred for 6 hours at a temperature of 90°C, labeled as Solution A. Similarly, 10 g PEG was dissolved in 80 mL of a 5% NaCl solution with a stirring of 6 hours at 90°C, labeled as Solution B. 50 mL of Solution A and Solution B were mixed and stirred for 6 hours at 90°C to obtain the HBE mixture. The HBE solution underwent degassing through ultrasonication at 60°C for 1 hour. Then, the solution was carefully poured into molds and refrigerated at -20°C for 12 hours. Subsequently, Solution A was cast on the surface of the frozen sample. After being stored at -20°C for 6 hours, the sample was naturally thawed for 12 hours. The freeze-thaw cycle was repeated three times to form the bilayer structure hydrogel. The preparation procedure for the PVA/PEG hydrogels was the same as that of HBE. However, the deionized water was used as the solvent instead of the 5% NaCl solution. Physical characterization of the hydrogel The microstructures of the hydrogel of the dehydrated HBE were characterized using a scanning electron microscope (SU8010, Hitachi, Japan). In order to test the mechanical properties, the HBE, HBE-1, and HBE-2 were sliced as film specimens, with 50 mm in length, 20 mm in width, and 2 mm in thickness. Subsequently, the mechanical properties of these hydrogels were evaluated utilizing an Instron universal material testing apparatus (INSTRON 3365, USA). The initial separation between clamps was meticulously set at 20 mm, while the loading rate was regulated at 10 mm/min. To examine the skin adhesion characteristics of hydrogels, fresh pigskin was sliced into rectangular strips with 200 mm in length, 40 mm in width, and 2 mm in thickness. These strips were then immersed in PBS to eliminate any residual contaminants. Similarly, the HBE was sliced into rectangular specimens with 100 mm in length, 20 mm in width, and 2 mm in thickness. The bonding area was configured at 70 × 20 mm² with an initial separation distance of 10 mm. The tissue adhesion force of the hydrogel was measured using an Instron universal material testing apparatus with a loading rate of 5 mm/min. In COMSOL Multiphysics simulation, the skin and hydrogel interface was simplified to a plane with surface roughness. The skin was set as the fixed bound while the interface between the hydrogel and skin was designated as a free surface in the model. Furthermore, the storage modulus (G′) and loss modulus (G″) of the HBE were assessed using a HAAKE MARS60 rheometer (Thermo-Fisher, USA). The oscillation frequency was from 0.1 Hz to 10 Hz, with a strain amplitude of 2%. In addition, the NETZSCH DMA 242 E dynamic thermomechanical analyzer was used to explore the dynamic behavior of G′ and G″ during a controlled heating process, spanning from 20°C to 60°C. The heating rate was calibrated at 5°C/min with an oscillation frequency of 5 Hz and a uniform strain amplitude of 2%. Electrochemical characterization Electrochemical impedance spectroscopy and cyclic voltammetry measurements were performed using a Gamry Reference 600 potentiostat/galvanostat/ZRA (Gamry Instruments, USA). EIS evaluations were performed within the frequency spectrum of 0.1 to 10 kHz. Cyclic voltammetry measurements were executed in the standard three-electrode configuration, utilizing Ag/AgCl (2 M KCl) as the reference electrode and an Au electrode, with a surface area of 1 cm², serving as the counter electrode. The signal transmission property was evaluated utilizing a TBS2000B digital oscilloscope (Tektronix, USA). Furthermore, the electrical properties, including the Current-Time curves of the HBE, were meticulously quantified with a digital Source Meter (Keithley 2400). All test samples were precisely dimensioned at 10 mm × 10 mm × 2 mm. Cell cultivation and biocompatibility L929 fibroblast cells (L929, Noblebio, Hangzhou, China), human epidermal keratinocyte cells (HaCat, Noblebio, Hangzhou, China), and human dermal fibroblasts (HDFs, Procell, Wuhan, China) were cultivated in a humidified chamber maintained at 37°C with an atmosphere with 5% CO 2 , utilizing DMEM (Procell, Wuhan, China) with 10% serum (Noblebio, Hangzhou, China). The cytotoxicity was quantified using the Cell Counting Kit-8 (CCK-8) assay (C0038, Beyotime Biotechnology, Shanghai, China). L929 cells were seeded at a density of 5 × 10 3 cells per well in 96-well plates, exposed to the hydrogel-extracted solution. The solution was replaced with CCK-8 reagent after 1, 2, and 3 days, respectively. After a 2-hour incubation at 37°C, the optical density (OD) was measured at 450 nm. The cell viability was determined by the formulation Cell viability = (OD n – OD c ) / (OD s – OD c ) × 100% where OD n represents the absorbance of the sample (hydrogel) group, OD c is the absorbance of the blank group, and OD s denotes the absorbance of the control group. The cytocompatibility of various hydrogel formulations was evaluated using the Live/Dead fluorescence staining kit (R37601, Invitrogen, USA). The hydrogel extract was prepared by immersing 0.1 g of hydrogel in 10 mL of culture medium for 24 hours. HaCat and HDFs were cultivated at a density of 2 × 10 4 cells per well in 24-well plates, exposed to the hydrogel-extracted solution. Subsequently, it is stained with the dual-parameter dye with an incubation of 1 and 3 days, respectively. After a 30-minute incubation, the cells were rinsed with phosphate-buffered saline (PBS) and examined under an inverted fluorescence microscope to discern live and dead cells. The blood compatibility of the hydrogels was assessed through an in vitro hemolysis assay. Freshly mouse blood was centrifuged at 3000 RPM for 15 mins at 4°C and the pellet was washed five times with PBS. The blood cells were then diluted to a concentration of 5% w/v and cultivated with the hydrogels for 1 hour at 37°C. After centrifugation at 3000 RPM for 10 minutes, the supernatant was collected. The absorbance was measured at 540 nm. The hemolysis rate was calculated by the formula, Hemolysis rate = (OD n – OD c ) / (OD s – OD c ) × 100% where OD n , OD c , and OD s are the absorbance of the supernatants with the treatment with the hydrogel, PBS solution, and deionized water, respectively. To evaluate the in vivo histocompatibility of the hydrogel, the rats were used as control and HBE samples. The HBE material was attached to the dorsum of the experimental group rats, and the skin reactions were monitored for 3 and 12 hours. After the removal of the material, a comprehensive examination was conducted utilizing hematoxylin and eosin (H&E), and Masson staining techniques to investigate the skin tissue and discern the inflammatory responses. EEG, MRI, and CT EEG signals were collected by a 32-channel system with the international 10–20 lead method and CPz was designated as the reference. The EEG signals were recorded using the eegoTM mylab (ANT Neuro, Enschede, Netherlands) at a sampling frequency of 1500 Hz. Both the reference and working electrodes employed in testing were the HBE hydrogel specifically developed in this study. The contact impedance between brain electrode and scalp was observed in real time during EEG signal detection (Fig. S3 , Supporting Information). MRI images and CT images of the subject, both with and without the HBE, were recorded using a clinical 3.0T-SIGNA™ Pioneer-70cm scanner (GE Healthcare, USA), and Brilliance CT Big Bore CT scanner (Philips, Netherlands). Declarations Acknowledgments The authors acknowledge the funding support from the National Natural Science Foundation of China (62204210, 62071463), the National Natural Science Foundation for Distinguished Young Scholars of China (62125112), the Natural Science Foundation of Jiangsu Province (BK20220284), and XJTLU Research Development Funding (RDF-21-01-027), Zhejiang Provincial Natural Science Foundation of China (LTGY24B050001) and Ningbo Natural Science Foundation (2022J252). Author details The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315046, P. R. China Guoqiang Ren, Liping Zhuang, Shunying Zhao, Jinxiu Guo, Zhaoxiang Peng, Jiangfan Lian, Botao Liu, Jingyun Ma, Xiaodong Hu, Zhewei Zhang and Mingming Hao School of CHIPS, XJTLU Entrepreneur College (Taicang), Xi’an Jiaotong-Liverpool University, Taicang, Suzhou, Jiangsu 215400, China Qifeng Lu, Mingxuan Zhang and Yinchao Zhao i -lab, Key Laboratory of Multifunctional Nanomaterials and Smart Systems, Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS), 398 Ruoshui Road, Suzhou, Jiangsu 215123, P. R. China Lianhui Li and Ting Zhang Author contributions M. H. and T. Z designed the project. R. G. and M. H. carried out the experiments. M. Z., L. Z., L. L., J. G., B. L., J. M., X. H., Z. Z., Y. X., and F. S. carried out the experiments discussed the methodology. S. Z., Z. P. and J. L. analyze the data. R. G., M. H., and Q. L. drafted the paper. Q. L., T. Z. and M. H. supervised the project. All the author reviewed the manuscript. Competing interests Prof. Ting Zhang is an Editor for the Journal, no other author has reported any competing interest Ethics approval and consent to participate Ethics approval and informed consent were obtained from all participants, and the protocol was approved by the Affiliated Lihuili Hospital of Ningbo University (KY2023SL036-02) and Ningbo University (12312). The study was carried out under the Helsinki Declaration. References Denny, J. C. & Collins, F. S. Precision medicine in 2030-seven ways to transform healthcare. Cell. 184, 1415–1419 (2021). Steinmetz, J. et al. Steinmetz J D, Seeher K M, Schiess N, et al. Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 23, 344–381 (2024). Ma, Q. et al. Temporal trend and attributable risk factors of stroke burden in China, 1990–2019: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 6, e897-e906 (2021). Wang, J. et al. Flexible Electrodes for Brain–Computer Interface System. Advanced Materials. 35, 2211012 (2023). Ma, J. et al. Hydrogel sensors for biomedical electronics. Chemical Engineering Journal. 481, 148317 (2024). Lin, S. et al. Advanced Electrode Technologies for Noninvasive Brain–Computer Interfaces. ACS Nano. 17, 24487–24513 (2023). Vázquez-Guardado, A., Yang, Y., Bandodkar, A. J. & Rogers, J. A. Recent advances in neurotechnologies with broad potential for neuroscience research. Nature Neuroscience. 23, 1522–1536 (2020). Zhang, M., Tang, Z., Liu, X. & Van der Spiegel, J. Electronic neural interfaces. Nature Electronics. 3, 191–200 (2020). Tang, X., Shen, H., Zhao, S., Li, N. & Liu, J. Flexible brain–computer interfaces. Nature Electronics. 6, 109–118 (2023). Yuk, H., Lu, B. & Zhao, X. Hydrogel bioelectronics. Chemical Society Reviews. 48, 1642–1667 (2019). Park, B. et al. Cuticular pad–inspired selective frequency damper for nearly dynamic noise–free bioelectronics. Science. 376, 624–629 (2022). Xue, H. et al. Hydrogel electrodes with conductive and substrate-adhesive layers for noninvasive long-term EEG acquisition. Microsystems & Nanoengineering. 9, 79 (2023). Liu, J. et al. Ten-hour stable noninvasive brain-computer interface realized by semidry hydrogel-based electrodes. Research. (2022). Wang, X. et al. Bioadhesive and conductive hydrogel-integrated brain-machine interfaces for conformal and immune-evasive contact with brain tissue. Matter. 5, 1204–1223 (2022). Liu, Y. et al. Body temperature enhanced adhesive, antibacterial, and recyclable ionic hydrogel for epidermal electrophysiological monitoring. Advanced Healthcare Materials. 11, 2200653 (2022). Yang, G. et al. Adhesive and hydrophobic bilayer hydrogel enabled on-skin biosensors for high‐fidelity classification of human emotion. Advanced Functional Materials. 32, 2200457 (2022). Tringides, C. M. et al. Viscoelastic surface electrode arrays to interface with viscoelastic tissues. Nature nanotechnology. 16, 1019–1029 (2021). Wei, W. et al. In situ multimodal transparent electrophysiological hydrogel for in vivo miniature two-photon neuroimaging and electrocorticogram analysis. Acta biomaterialia. 152, 86–99 (2022). Yuk, H., Zhang, T., Lin, S., Parada, G. A. & Zhao, X. Tough bonding of hydrogels to diverse non-porous surfaces. Nature materials. 15, 190–196 (2016). Luo, J. et al. MXene-enabled self-adaptive hydrogel interface for active electroencephalogram interactions. ACS nano. 16, 19373–19384 (2022). Lyu, C. et al. Bone-inspired (GNEC/HAPAAm) hydrogel with fatigue-resistance for use in underwater robots and highly piezoresistive sensors. Microsystems & Nanoengineering. 9, 99 (2023). Hao, M. et al. Tough engineering hydrogels based on swelling–freeze–thaw method for artificial cartilage. ACS Applied Materials & Interfaces. 14, 25093–25103 (2022). Shin, Y. et al. Low-impedance tissue-device interface using homogeneously conductive hydrogels chemically bonded to stretchable bioelectronics. Science Advances. 10, eadi7724 (2024). Zhang, D. et al. Stretchable and durable HD-sEMG electrodes for accurate recognition of swallowing activities on complex epidermal surfaces. Microsystems & Nanoengineering. 9, 115 (2023). Zhang, J. et al. Engineering electrodes with robust conducting hydrogel coating for neural recording and modulation. Advanced Materials. 35, 2209324 (2023). Tang, H. et al. Multifunctional Conductive Hydrogel Interface for Bioelectronic Recording and Stimulation. Advanced Healthcare Materials. 2400562 (2024). Wang, C. et al. On-skin paintable biogel for long-term high-fidelity electroencephalogram recording. Science Advances. 8, eabo1396 (2022). Won, D. et al. Laser-induced wet stability and adhesion of pure conducting polymer hydrogels. Nature Electronics. (2024). Han, Q. et al. Hydrogel Nanoarchitectonics of a Flexible and Self-Adhesive Electrode for Long‐Term Wireless Electroencephalogram Recording and High‐Accuracy Sustained Attention Evaluation. Advanced Materials. 35, 2209606 (2023). Wang, X. et al. Subdural neural interfaces for long-term electrical recording, optical microscopy and magnetic resonance imaging. Biomaterials. 281, 121352 (2022). Chen, Z. et al. Multimodal optoacoustic imaging: methods and contrast materials. Chemical Society Reviews. 53, 6068 (2024). Ducharme, S. Brain MRI research in neurodegenerative dementia: time to deliver on promises. Brain. 146, 4403–4404 (2023). Barrière, D. et al. The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization. Nature communications. 10, 1–13 (2019). Shribman, S. et al. Neuroimaging correlates of brain injury in Wilson’s disease: a multimodal, whole-brain MRI study. Brain. 145, 263–275 (2022). Tian, L. et al. Large-area MRI-compatible epidermal electronic interfaces for prosthetic control and cognitive monitoring. Nature biomedical engineering. 3, 194–205 (2019). Additional Declarations (Not answered) Supplementary Files MRIandCTcompatiblehydrogelSI.docx ethicsanimal.pdf ethicshuman.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: revise 31 Jul, 2024 Review # 3 received at journal 27 Jul, 2024 Review # 2 received at journal 16 Jul, 2024 Reviewer # 3 agreed at journal 16 Jul, 2024 Review # 1 received at journal 15 Jul, 2024 Reviewer # 2 agreed at journal 10 Jul, 2024 Reviewer # 1 agreed at journal 10 Jul, 2024 Reviewers invited by journal 10 Jul, 2024 Submission checks completed at journal 01 Jul, 2024 First submitted to journal 01 Jul, 2024 Unknown event 30 Jun, 2024 Editor assigned by journal 29 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4657809","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":325130121,"identity":"e32e9103-421a-4537-8ed6-7f301558b556","order_by":0,"name":"Qifeng Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYDACZsYHIEqGgb2BwYChAMROIKSF2QBE8TDwHGAwOGBAjBYGmBYJoEqitPAdZ2Z8XPCLgcfg5huD4g8Ghxn42XMMGH7uwK1F8jAzs/HMPqCW22kJQIcdZpDseWPA2HsGtxaDw/zHpHl7QFqSD4C1GNzIMWBmbMOnhZn9N1jLzYMNYC32RGhhY+b5AdRygxlqiwQBLSC/SPM2SPBIngH65YxBOo/EmWcFB3vxaOE7f5jxM88fGzm+42fMDCoqrOX425M3PviJRwvDASBmbJMAMdlAscIDE8SvheEPmMn8AK/KUTAKRsEoGLEAAP4BTJJDt12+AAAAAElFTkSuQmCC","orcid":"","institution":"Xi'an Jiaotong-Liverpool University","correspondingAuthor":true,"prefix":"","firstName":"Qifeng","middleName":"","lastName":"Lu","suffix":""},{"id":325130122,"identity":"96a9565d-139b-4d66-bd53-e7d4a75e6c5f","order_by":1,"name":"Guoqiang Ren Ren","email":"","orcid":"","institution":"The Affiliated Lihuili Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Guoqiang","middleName":"Ren","lastName":"Ren","suffix":""},{"id":325130124,"identity":"ca9afc6e-ec85-4d8a-b1ba-9903e2bb5eb5","order_by":2,"name":"Mingxuan Zhang","email":"","orcid":"","institution":"Xi’an Jiaotong-Liverpool University","correspondingAuthor":false,"prefix":"","firstName":"Mingxuan","middleName":"","lastName":"Zhang","suffix":""},{"id":325130127,"identity":"efb786c4-0398-4430-ba26-18df26d2d59e","order_by":3,"name":"Liping Zhuang","email":"","orcid":"","institution":"The Affiliated Lihuili Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Liping","middleName":"","lastName":"Zhuang","suffix":""},{"id":325130128,"identity":"30eee769-ecdc-4381-971c-bcd0237acfde","order_by":4,"name":"Lianhui Li","email":"","orcid":"","institution":"Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of Sciences, Suzhou 215123, China","correspondingAuthor":false,"prefix":"","firstName":"Lianhui","middleName":"","lastName":"Li","suffix":""},{"id":325130129,"identity":"670fe3c5-ff54-4d00-a857-98533b6cf642","order_by":5,"name":"Shunying Zhao","email":"","orcid":"","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Shunying","middleName":"","lastName":"Zhao","suffix":""},{"id":325130130,"identity":"1715f04a-13ed-4f06-9460-fdd22b57be82","order_by":6,"name":"Jinxiu Guo","email":"","orcid":"","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Jinxiu","middleName":"","lastName":"Guo","suffix":""},{"id":325130131,"identity":"267c7c7f-2489-4935-8de2-c5a282c8b990","order_by":7,"name":"Yinchao Zhao","email":"","orcid":"","institution":"Xi’an Jiaotong-Liverpool University","correspondingAuthor":false,"prefix":"","firstName":"Yinchao","middleName":"","lastName":"Zhao","suffix":""},{"id":325130132,"identity":"22585ee3-f6d3-4d18-b190-348a6d9565c8","order_by":8,"name":"zhaoxiang Peng","email":"","orcid":"","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"zhaoxiang","middleName":"","lastName":"Peng","suffix":""},{"id":325130133,"identity":"c76e4625-32ec-48c5-af49-e2b435cacbe8","order_by":9,"name":"Jiangfang Lian","email":"","orcid":"","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Jiangfang","middleName":"","lastName":"Lian","suffix":""},{"id":325130134,"identity":"46b7f6ba-ea62-48b4-99ef-26a3fa70a295","order_by":10,"name":"Botao Liu","email":"","orcid":"https://orcid.org/0000-0001-9305-8380","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Botao","middleName":"","lastName":"Liu","suffix":""},{"id":325130135,"identity":"42ac3fb0-4719-4044-842f-af730404c962","order_by":11,"name":"Jingyun Ma","email":"","orcid":"","institution":"The Affiliated Lihuili Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Jingyun","middleName":"","lastName":"Ma","suffix":""},{"id":325130136,"identity":"e12f2503-dce3-492e-97c6-4d66f3817f87","order_by":12,"name":"Xiaodong Hu","email":"","orcid":"","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Xiaodong","middleName":"","lastName":"Hu","suffix":""},{"id":325130137,"identity":"bbbb5ea7-b22a-4a7c-bd18-1cb5b7c99ffc","order_by":13,"name":"Zhewei Zhang","email":"","orcid":"","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Zhewei","middleName":"","lastName":"Zhang","suffix":""},{"id":325130138,"identity":"e09e26d0-3972-46ea-a366-56ccd7e5856c","order_by":14,"name":"Ting Zhang","email":"","orcid":"","institution":"Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS)","correspondingAuthor":false,"prefix":"","firstName":"Ting","middleName":"","lastName":"Zhang","suffix":""},{"id":325130139,"identity":"2d0729c5-0ec1-47a7-b4bf-b8873672e8d9","order_by":15,"name":"Mingming Hao","email":"","orcid":"","institution":"The Affiliated LiHuiLi Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Mingming","middleName":"","lastName":"Hao","suffix":""}],"badges":[],"createdAt":"2024-06-29 06:25:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4657809/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4657809/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62159319,"identity":"312c98d6-9b1a-4bd3-9b1a-461fda81f7c2","added_by":"auto","created_at":"2024-08-09 21:45:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":6372958,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of brain activity recording and microstructure morphology of the hydrogel EEG electrode. (A) Schematic diagram of brain activity recording. (B) SEM images of the hydrogel EEG electrode with the microstructure morphology of the two layers with different moduli. (C) Testing of the hydrogel EEG electrode in clinical applications, including CT and MRI environments.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/a21480b94365ad93ae8be166.png"},{"id":62158960,"identity":"0d71c286-399f-48d5-b547-3dc136c967fd","added_by":"auto","created_at":"2024-08-09 21:37:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":537580,"visible":true,"origin":"","legend":"\u003cp\u003eMechanical properties of the hydrogel. (A) Stress-strain curves of HBE-1, HBE-2, and the bilayer HBE hydrogel at different tensile strains. (B) Cyclic stress-strain curves of HBE-1, HBE-2, and the HBE hydrogel at a tensile strain of 100%. (C) The Young’s moduli of HBE-1, HBE-2, and the HBE hydrogel. (D) Rheological properties of HBE-1, HBE-2, and the HBE hydrogel at tensile strain frequencies of 0.1~10Hz. (E)-(F) Rheological properties of HBE-1, HBE-2, and the HBE hydrogel at temperatures ranging from 25 to 60 °C.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/48af6841c9670600a12ca9c4.png"},{"id":62158963,"identity":"5d9b84a6-1a09-4961-bdd3-63e78aa7e746","added_by":"auto","created_at":"2024-08-09 21:37:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":4041949,"visible":true,"origin":"","legend":"\u003cp\u003eAdhesion performance of the hydrogel. (A)-(F) COMSOL simulation of the adhesion stress distribution of the hydrogel on the surface of the skin. (G) 90-degree peel adhesion strength test. (H) Adhesion optical images on the wrist and fingers of a human subject.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/ef8db832463d6ff21489252a.png"},{"id":62158961,"identity":"46fb13ce-3a6a-490c-8829-63b334c476fa","added_by":"auto","created_at":"2024-08-09 21:37:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1152423,"visible":true,"origin":"","legend":"\u003cp\u003eElectrical properties of the hydrogel-based EEG electrodes. (A)-(C) EIS spectra, phase angle, and frequency response of HBE, HBE-1, and HBE-2. (D) Conductivity of the HBE electrode at different times. (E) Cyclic voltammetry curves of HBE, HBE-1, and HBE-2. (F) Cyclic voltammetry curves of HBE under different strains. (G) long-term stability of the hydrogel. (H)-(I) Input and output voltage waveforms of HBE with different frequencies.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/7270cab6ae3f57fc85e05e35.png"},{"id":62158962,"identity":"e00f7859-571b-40fc-a695-6e726c61f5c8","added_by":"auto","created_at":"2024-08-09 21:37:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":4595265,"visible":true,"origin":"","legend":"\u003cp\u003eCytocompatibility and hemocompatibility of the hydrogels. (A) Cell viability of L929 cells treated with different hydrogels for 1, 2, and 3 days. (B) Hemolysis photographs and Hemolysis ratio (%) of the hydrogels. (C) and (D) Live/Dead staining of Hacat and human dermal fibroblasts after being treated with different hydrogels for 1, 2, and 3 days. (E) Masson's trichrome and H\u0026amp;E staining of skin tissues after being treated with HBE hydrogel for 3 and 12 hours.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/c034097e10231754a82adad5.png"},{"id":62158965,"identity":"b1559ee6-ca01-45c1-a1ed-995953d17e9d","added_by":"auto","created_at":"2024-08-09 21:37:09","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":4600780,"visible":true,"origin":"","legend":"\u003cp\u003eThe testing of EEG signals from the subjects with the hydrogel EEG electrodes. (A) The test in a relaxed state, deep breathing, and flashing light stimulation. (B) EEG waveform depicting the brain electrical signals in different states. (C) Brain topography maps of the spatial distribution of brain electrical activity at different states (relaxation, deep breathing, 10Hz frequency flashing light stimulation, and 30Hz frequency flashing light stimulation).\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/3cde87c12c1dbcd8990f421a.png"},{"id":62158967,"identity":"f7f977ab-478c-4b1b-80cc-172b66cf85b7","added_by":"auto","created_at":"2024-08-09 21:37:09","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":3888255,"visible":true,"origin":"","legend":"\u003cp\u003eThe CT and MRI of the brain. (A) A1 and A2 show the brain images of the subject undergoing CT scans with and without wearing hydrogel brain electrodes. (B) B1 and B2 present the brain images of the subject undergoing MRI scans with and without wearing hydrogel electrodes.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/5132db07547766b0d990834f.png"},{"id":62159329,"identity":"691fece5-cbeb-43de-90c8-4c6b1928fbe3","added_by":"auto","created_at":"2024-08-09 21:45:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":28066027,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/54194bde-25a8-407f-9421-97f57481c037.pdf"},{"id":62158964,"identity":"5a457f73-6892-4242-b2fe-1cb077b8172f","added_by":"auto","created_at":"2024-08-09 21:37:09","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":703151,"visible":true,"origin":"","legend":"","description":"","filename":"MRIandCTcompatiblehydrogelSI.docx","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/d4133a61a8a03371389bec88.docx"},{"id":62158968,"identity":"cfa16121-aedf-4160-88a5-895abd1c4b16","added_by":"auto","created_at":"2024-08-09 21:37:09","extension":"pdf","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":426908,"visible":true,"origin":"","legend":"","description":"","filename":"ethicsanimal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/f8a809cb939f98143cf79ced.pdf"},{"id":62158969,"identity":"1228a162-87bf-468d-8042-3fad6463fadb","added_by":"auto","created_at":"2024-08-09 21:37:09","extension":"pdf","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":1383967,"visible":true,"origin":"","legend":"","description":"","filename":"ethicshuman.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4657809/v1/2d92b19c7fecb9606f36e97f.pdf"}],"financialInterests":"(Not answered)","formattedTitle":"MRI and CT Compatible Asymmetric Bilayer Hydrogel Electrodes for EEG-Based Brain Activity Monitoring","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the World Health Organization (WHO), approximately one-third of the global population experiences neurological disorders, which are the leading causes of health loss and disability worldwide \u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The diagnosis of neurological disorders is realized by the acquisition and analysis of electroencephalogram (EEG) signals due to its non-invasive property as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA. This approach is pivotal for managing neurological conditions and ensuring high-quality care, treatment, and rehabilitation services for patients \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. However, EEG signals, characterized by frequencies from 0.5 to 100 Hz and amplitudes ranging from 1 to 200 \u0026micro;V, are prone to attenuation and distortion due to impedance mismatch when transmitted through subcutaneous tissues to the brain interface \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Moreover, human body movement generates additional interference to the EEG signals \u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Consequently, the development of EEG electrodes capable of long-term signal collection is crucial for precision medical testing in neural diseases \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIonic conductive hydrogel, a soft material renowned for its excellent moisture retention and unique ion transport mechanism, is ideal for flexible devices and systems with high stretchability, conformal adhesion, noise filtration, and compatibility \u003csup\u003e\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Consequently, a number of studies have been conducted on hydrogel electrodes \u003csup\u003e\u003cspan additionalcitationids=\"CR24 CR25 CR26\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Seung Hwan Ko's team utilized PEDOT: PSS as a conductive filler to create high-stability conductive hydrogels that adhere to various substrates through laser-induced phase separation and interface structures. This method enables the selective transformation of conducting polymers into conductive hydrogels with wet conductivities of 101.4 S/cm and patterning with a spatial resolution as fine as 5 \u0026micro;m \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Yan and Zhang explored the development of a highly conductive, viscoelastic, and biocompatible hydrogel, capable of establishing an efficient and stable interface between human tissue and electrodes, yielding high-quality EEG signals via a non-invasive approach \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. In collaboration with Suo, Wang introduced an implantable subdural cortical electrode with high transparency and low modulus, compatible with optogenetic equipment for multidimensional brain information detection in animal models \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. However, the single-mode EEG signal suffers from low spatial resolution and has an impact on the feature identification accuracy. While CT and MRI offer higher spatial resolution for brain structural and functional signals, their strong magnetic fields significantly interference with EEG sensors \u003csup\u003e\u003cspan additionalcitationids=\"CR32 CR33 CR34\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. Consequently, The EEG electrodes, which is able to record EEG with CT and MRI images simultaneously has yet to be reported.\u003c/p\u003e \u003cp\u003eIn this research, an asymmetrical bilayer hydrogel EEG electrode was proposed, featuring a lower modulus layer (HBE-1) and a higher modulus upper layer (HBE-2) in its structure as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB. The bilayer design endows the hydrogel with high conductivity, flexibility, and biocompatibility. Therefore, the high-quality EEG signals can be collected. In addition, benefited from metal-free property, the ionic conductive hydrogel is compatible with strong magnetic fields, which ensures its suitability in operation of CT and MRI environments. As a demonstration, the integration of EEG with CT/MRI was achieved for the EEG signal and brain structural image recording as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC. This method facilitates high temporal and spatial resolution brain disease examinations. The research outcomes offer a novel approach for multi-dimensional brain information monitoring and the diagnosis of brain diseases.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Result and Discussions","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMechanical properties of the hydrogel\u003c/h2\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the mechanical performance of the hydrogel under different strain and temperature conditions. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-C demonstrate that HBE-1 exhibits higher adhesion force within a lower strain range and has a low Young\u0026rsquo;s modulus of 0.12\u0026thinsp;~\u0026thinsp;0.15 MPa. In contrast, HBE-2 shows higher flexibility and toughness within a higher strain range, with a high Young\u0026rsquo;s modulus of 0.35\u0026thinsp;~\u0026thinsp;0.38 MPa. The bilayer structure of HBE has the advantages of both layers with the Young\u0026rsquo;s modulus between that of HBE-1 and HBE-2 (0.22\u0026thinsp;~\u0026thinsp;0.28 MPa). The storage modulus of HBE-1 in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD indicates its high flexibility under dynamic conditions within the 0.1\u0026thinsp;~\u0026thinsp;10Hz tensile vibration frequency. HBE-2 exhibits the highest storage modulus as well as a higher loss modulus, which indicates its higher rigidity and energy dissipation under dynamic conditions. The storage modulus and loss modulus of HBE are between those of HBE-1 and HBE-2. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF illustrate that HBE-2 shows the smallest variation in complex modulus under different temperatures. The results demonstrate its good stability under various temperature conditions. The static and dynamic mechanical performance of the hydrogel can provide evidence for the selection of appropriate hydrogel layers based on the requirements. The HBE has good resistance to water loss within 48 hours (Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e, Supporting Information). For applications with higher demands for comprehensive performance in clinical applications, the bilayer structure of HBE can be adopted to ensure the stable recording of signals.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAdhesion properties of the hydrogel\u003c/h3\u003e\n\u003cp\u003eThe adhesion property of the hydrogel electrode is crucial for stable and reliable EEG signal monitoring, which is the fundamental requirement for accurate data collection and comfortable long-term wear. Therefore, the adhesion model of the hydrogel electrode on the surface of the skin was established by COMSOL. The adhesion process of the electrode on the skin surface and the distribution of adhesion strength were investigated and shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-F. In detail, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD show the deformation of the hydrogel on the skin under tension, which demonstrates that the hydrogel undergoes maximum tensile deformation at the center of the skin strain according to simulation results. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE illustrate the stress distribution and adhesion strength changes resulting from the stretch of the hydrogel. The results indicate that no significant impact was observed on the contact area with the skin surface. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF demonstrate the effect of the tensile deformation of the hydrogel. Simulation results show that the hydrogel exhibits uniform adhesion stress distribution on the skin surface which enables the stable attachment to biological tissue without significant stress during stretching.\u003c/p\u003e \u003cp\u003eA 90-degree peel test was conducted using the Instron universal material testing machine at a loading rate of 5mm/min. The peel adhesion strength of the hydrogel gradually increases within the displacement range of 0\u0026thinsp;~\u0026thinsp;60 mm and reaches a maximum value of approximately 45 kPa as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eG. The peel test results indicate that the hydrogel exhibits high peel adhesion strength and maintains stable adhesion performance within a large displacement range. In addition, the hydrogel was adhered to the wrist and fingers of the subjects to investigate the adhesion property during the bending and stretching states as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eH. The findings demonstrate that the hydrogel can stably adhere to the wrists and fingers of individuals during movement, indicating its potential for long-term wearable and flexible systems.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eElectrical properties of hydrogel-based EEG electrodes\u003c/h2\u003e \u003cp\u003eThe electrical impedance of the hydrogel-based EEG electrodes is also a crucial parameter in signal fidelity and reliability, which is important for neurophysiological studies. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA shows the electrical impedance spectra (EIS) of Au, HBE, HBE-1, and HBE-2 electrodes. The impedance of the Au electrode is significantly higher than that of the HBE electrode, indicating the better ion conductivity of the HBE electrode. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB illustrates the phase angle variation with frequency. The phase angle of the HBE electrode approaches 90 degrees in the low-frequency range, suggesting stronger capacitive behavior. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC displays the impedance variation with frequency. The impedance of the HBE electrode is significantly lower than that of the Au electrode, reaching the lowest impedance value after 1 hour. In Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD, the conductivity remains steady at approximately 0.7\u0026ndash;0.9 S/m with no significant decrease in the conductivity observed within the following one hour. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eE presents the cyclic voltammetry curves of the HBE, HBE-1, and HBE-2 electrodes. The current response of the HBE electrode is significantly higher than that of the single-layer hydrogel electrode, HBE-2, indicating its superior comprehensive conductive performance. The cyclic voltammetry curves of the HBE electrode at different tensile strains of 0%, 20%, and 50% were performed to test the reliability of the electrode during movement. As depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eF, no significant change was observed. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eG demonstrates the long-term stability of the HBE electrode, showing that the electrode can work stably for more than 12 hours. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eH-I show the input and output voltage waveforms at different frequencies, indicating that the HBE electrodes can effectively respond to the input signals up to 10 kHz.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eBiocompatibility of the EEG electrodes\u003c/h2\u003e \u003cp\u003eBiocompatibility is a crucial factor for hydrogel electrodes to be used in biological systems without adverse effects. Therefore, cytocompatibility and hemocompatibility were investigated in our research. The cytocompatibility of the CCK8 cell viability assay is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA. Both the PVA/PEG and HBE materials sustained cell viability exceeding 90% over 1, 2, and 3 days, which is close to the PBS control group. This result indicates the minimal cytotoxicity towards L929 fibroblasts. In Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB, the hemolysis rate of the HBE material is notably lower than that of Triton X-100 (positive control), which indicates that no significant difference between the hydrogel and the PBS control group. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC and Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD present the results of the Live/Dead immunofluorescence staining. The HaCaT cells and human dermal fibroblasts within the PVA/PEG and HBE material groups exhibit vigorous growth, elevated cell density, and uncompromised morphology over 1, 2, and 3 days, without any appreciable discrepancies from the control group. This result confirms the exceptional cytocompatibility of the material. The hematoxylin and eosin (H\u0026amp;E) and Masson staining shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE reveal that the skin tissue remained unperturbed after the application of the HBE to the rat dorsum for 3 and 12 hours. No discernible influx of inflammatory cells or tissue perturbation was observed, indicating that the HBE material does not provoke skin irritation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eEEG signals recorded by hydrogel-based electrodes\u003c/h2\u003e \u003cp\u003eAfter investigating the basic electrical and mechanical properties of the hydrogel, we conducted the EEG signal monitoring with the hydrogel-based electrodes and analyzed the EEG signals and brain topography. Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA depicts the EEG signal recording in a relaxed sitting state, deep breathing in a sitting position, and exposure to a flashing light. From the energy spectrum, correlation distribution, and amplitude from EEG signals and brain topography in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB and Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eC, the EEG signals appear relatively stable, with minimal potential fluctuations across all channels, which indicates low brain activity of the subjects in the relaxed state. Representative EEG signals in 295 to 299 seconds with HBE electrodes (Fig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e, Supporting Information). The analysis of brain topography and energy spectrum confirms that the signals concentrated in the 0.5-4.0 Hz (Delta waves) and 4.0\u0026ndash;8.0 Hz (Theta waves) frequency ranges are mainly associated with relaxation. During deep breathing, noticeable rhythmic changes in the EEG waveforms are observed, which is consistent with the respiratory frequency. The energy spectrum in the 4.0\u0026ndash;8.0 Hz (Theta waves) and 8.0\u0026ndash;13.0 Hz (Alpha waves) frequency bands reflect the significant impact of deep breathing on brain electrical activity. In addition, there is a slight coherence increase than that in the relaxed state, which can be attributed to the enhanced brain activity. Under flashing light with a frequency of 10 Hz, a strong synchronized response is observed in the EEG waveforms. Significant enhancement in brain electrical activity appears in the 8.0\u0026ndash;13.0 Hz (Alpha waves) and 13.0\u0026ndash;30.0 Hz (Beta waves), accompanied by a noteworthy increase in coherence in the Alpha and Beta bands. The amplitudes are significantly enhanced due to the substantial brain electrical response to flashing light frequency. When the flashing frequency increases to 30 Hz, the EEG waveforms exhibit pronounced synchronized patterns with significant enhancement in brain activity observed in the 13.0\u0026ndash;30.0 Hz (Beta waves) frequency band. The amplitudes also significantly increase, indicating a notable impact of the flashing frequency of the light on high-frequency brain electrical activity.\u003c/p\u003e \u003cp\u003eThe analysis of EEG signals with the brain topography shows that the Delta and Theta waves are concentrated in the forehead, while Alpha and Beta waves are lower and evenly distributed across the scalp, signifying uniform electrical activity in these bands across the entire head. High coherence in the 0.5-4.0 Hz frequency range, especially in the forehead, indicates strong synchronized activity in the low-frequency range in the forehead. Low coherence in the 4.0\u0026ndash;30.0 Hz frequency range suggests poor synchronization of electrical activity across different regions. The high amplitudes distributed in the middle and anterior regions of the head indicate greater electrical activity strength in these areas. The energy spectrum, coherence distribution, and amplitude of brain electrical activity under different states and stimuli in the research show potential for providing a comprehensive foundation for clinical examinations, diagnosis, and treatment recommendations for brain disease.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCompatibility of hydrogel-based EEG electrodes in CT and MRI environment\u003c/h2\u003e \u003cp\u003eFinally, the compatibility of the EEG hydrogel electrode with MRI and CT was conducted to demonstrate its potential application in clinical diagnosis. The CT images Fig.\u0026nbsp;7A1 and Fig.\u0026nbsp;7A2 of display the skull and brain structures. In contrast to the metal electrodes, no interference with the imaging is observed in the presence of the hydrogel electrodes. Figure\u0026nbsp;7B1 and B2 present the brain tissue structures with hydrogel electrodes, and almost no impact on the quality of the MRI images, such as magnetic resonance artifacts, was observed. The result indicates that the hydrogel electrodes can be used in both CT and MRI environments without the issues of artifacts as in traditional metal electrodes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe hydrogel, a soft and biocompatible material, has a great potential in flexible and wearable systems for long-term monitoring of biological signals with comfort and no skin irritation. In this study, an asymmetric bilayer hydrogel was designed and synthesized for EEG electrodes. The top layer, characterized by a high modulus, ensures high conductivity, whereas the bottom layer, with a low modulus, improves wearing comfort and skin conformality. This bilayer design not only enhances interface contact but also maintains structural stability. High-quality EEG signals were successfully recorded in various states, including relaxation, deep breathing, and flash stimulation. In addition, the metal-free nature of the hydrogel electrodes allows compatibility with CT and MRI without generating artifacts. Consequently, the proposed hydrogel-based electrodes provide substantial benefits for monitoring complex brain activities and shows a potential in simultaneous recording of multi-dimensional brain activity. The research findings lay a foundation for the comprehensive study of brain diseases and brain science.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMaterials\u003c/h2\u003e \u003cp\u003ePolyvinyl alcohol (PVA-117, Mw\u0026thinsp;~\u0026thinsp;145, 000), Polyethylene glycol (Average Mn 4, 000), and NaCl (Medical grade) were sourced from Shanghai Aladdin Industrial Corporation Co. Ltd. All other materials, unless specified, were commercially available and used as received. The deionized water utilized in the experiments consistently met Milli-Q grade standards with a resistivity of 18.2 MΩ.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSynthesis of HBE and PVA/PEG Hydrogel\u003c/h2\u003e \u003cp\u003e20 g PVA was dissolved in 80 mL of a 5% NaCl solution and the solution was stirred for 6 hours at a temperature of 90\u0026deg;C, labeled as Solution A. Similarly, 10 g PEG was dissolved in 80 mL of a 5% NaCl solution with a stirring of 6 hours at 90\u0026deg;C, labeled as Solution B. 50 mL of Solution A and Solution B were mixed and stirred for 6 hours at 90\u0026deg;C to obtain the HBE mixture. The HBE solution underwent degassing through ultrasonication at 60\u0026deg;C for 1 hour. Then, the solution was carefully poured into molds and refrigerated at -20\u0026deg;C for 12 hours. Subsequently, Solution A was cast on the surface of the frozen sample. After being stored at -20\u0026deg;C for 6 hours, the sample was naturally thawed for 12 hours. The freeze-thaw cycle was repeated three times to form the bilayer structure hydrogel. The preparation procedure for the PVA/PEG hydrogels was the same as that of HBE. However, the deionized water was used as the solvent instead of the 5% NaCl solution.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePhysical characterization of the hydrogel\u003c/h2\u003e \u003cp\u003eThe microstructures of the hydrogel of the dehydrated HBE were characterized using a scanning electron microscope (SU8010, Hitachi, Japan). In order to test the mechanical properties, the HBE, HBE-1, and HBE-2 were sliced as film specimens, with 50 mm in length, 20 mm in width, and 2 mm in thickness. Subsequently, the mechanical properties of these hydrogels were evaluated utilizing an Instron universal material testing apparatus (INSTRON 3365, USA). The initial separation between clamps was meticulously set at 20 mm, while the loading rate was regulated at 10 mm/min. To examine the skin adhesion characteristics of hydrogels, fresh pigskin was sliced into rectangular strips with 200 mm in length, 40 mm in width, and 2 mm in thickness. These strips were then immersed in PBS to eliminate any residual contaminants. Similarly, the HBE was sliced into rectangular specimens with 100 mm in length, 20 mm in width, and 2 mm in thickness. The bonding area was configured at 70 \u0026times; 20 mm\u0026sup2; with an initial separation distance of 10 mm. The tissue adhesion force of the hydrogel was measured using an Instron universal material testing apparatus with a loading rate of 5 mm/min. In COMSOL Multiphysics simulation, the skin and hydrogel interface was simplified to a plane with surface roughness. The skin was set as the fixed bound while the interface between the hydrogel and skin was designated as a free surface in the model. Furthermore, the storage modulus (G\u0026prime;) and loss modulus (G\u0026Prime;) of the HBE were assessed using a HAAKE MARS60 rheometer (Thermo-Fisher, USA). The oscillation frequency was from 0.1 Hz to 10 Hz, with a strain amplitude of 2%. In addition, the NETZSCH DMA 242 E dynamic thermomechanical analyzer was used to explore the dynamic behavior of G\u0026prime; and G\u0026Prime; during a controlled heating process, spanning from 20\u0026deg;C to 60\u0026deg;C. The heating rate was calibrated at 5\u0026deg;C/min with an oscillation frequency of 5 Hz and a uniform strain amplitude of 2%.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eElectrochemical characterization\u003c/h2\u003e \u003cp\u003eElectrochemical impedance spectroscopy and cyclic voltammetry measurements were performed using a Gamry Reference 600 potentiostat/galvanostat/ZRA (Gamry Instruments, USA). EIS evaluations were performed within the frequency spectrum of 0.1 to 10 kHz. Cyclic voltammetry measurements were executed in the standard three-electrode configuration, utilizing Ag/AgCl (2 M KCl) as the reference electrode and an Au electrode, with a surface area of 1 cm\u0026sup2;, serving as the counter electrode. The signal transmission property was evaluated utilizing a TBS2000B digital oscilloscope (Tektronix, USA). Furthermore, the electrical properties, including the Current-Time curves of the HBE, were meticulously quantified with a digital Source Meter (Keithley 2400). All test samples were precisely dimensioned at 10 mm \u0026times; 10 mm \u0026times; 2 mm.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCell cultivation and biocompatibility\u003c/h2\u003e \u003cp\u003eL929 fibroblast cells (L929, Noblebio, Hangzhou, China), human epidermal keratinocyte cells (HaCat, Noblebio, Hangzhou, China), and human dermal fibroblasts (HDFs, Procell, Wuhan, China) were cultivated in a humidified chamber maintained at 37\u0026deg;C with an atmosphere with 5% CO\u003csub\u003e2\u003c/sub\u003e, utilizing DMEM (Procell, Wuhan, China) with 10% serum (Noblebio, Hangzhou, China). The cytotoxicity was quantified using the Cell Counting Kit-8 (CCK-8) assay (C0038, Beyotime Biotechnology, Shanghai, China). L929 cells were seeded at a density of 5 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e cells per well in 96-well plates, exposed to the hydrogel-extracted solution. The solution was replaced with CCK-8 reagent after 1, 2, and 3 days, respectively. After a 2-hour incubation at 37\u0026deg;C, the optical density (OD) was measured at 450 nm. The cell viability was determined by the formulation\u003c/p\u003e \u003cp\u003eCell viability = (OD\u003csub\u003en\u003c/sub\u003e \u0026ndash; OD\u003csub\u003ec\u003c/sub\u003e) / (OD\u003csub\u003es\u003c/sub\u003e \u0026ndash; OD\u003csub\u003ec\u003c/sub\u003e) \u0026times; 100%\u003c/p\u003e \u003cp\u003ewhere OD\u003csub\u003en\u003c/sub\u003e represents the absorbance of the sample (hydrogel) group, OD\u003csub\u003ec\u003c/sub\u003e is the absorbance of the blank group, and OD\u003csub\u003es\u003c/sub\u003e denotes the absorbance of the control group.\u003c/p\u003e \u003cp\u003eThe cytocompatibility of various hydrogel formulations was evaluated using the Live/Dead fluorescence staining kit (R37601, Invitrogen, USA). The hydrogel extract was prepared by immersing 0.1 g of hydrogel in 10 mL of culture medium for 24 hours. HaCat and HDFs were cultivated at a density of 2 \u0026times; 10\u003csup\u003e4\u003c/sup\u003e cells per well in 24-well plates, exposed to the hydrogel-extracted solution. Subsequently, it is stained with the dual-parameter dye with an incubation of 1 and 3 days, respectively. After a 30-minute incubation, the cells were rinsed with phosphate-buffered saline (PBS) and examined under an inverted fluorescence microscope to discern live and dead cells.\u003c/p\u003e \u003cp\u003eThe blood compatibility of the hydrogels was assessed through an in vitro hemolysis assay. Freshly mouse blood was centrifuged at 3000 RPM for 15 mins at 4\u0026deg;C and the pellet was washed five times with PBS. The blood cells were then diluted to a concentration of 5% w/v and cultivated with the hydrogels for 1 hour at 37\u0026deg;C. After centrifugation at 3000 RPM for 10 minutes, the supernatant was collected. The absorbance was measured at 540 nm. The hemolysis rate was calculated by the formula,\u003c/p\u003e \u003cp\u003eHemolysis rate = (OD\u003csub\u003en\u003c/sub\u003e \u0026ndash; OD\u003csub\u003ec\u003c/sub\u003e) / (OD\u003csub\u003es\u003c/sub\u003e \u0026ndash; OD\u003csub\u003ec\u003c/sub\u003e) \u0026times; 100%\u003c/p\u003e \u003cp\u003ewhere OD\u003csub\u003en\u003c/sub\u003e, OD\u003csub\u003ec\u003c/sub\u003e, and OD\u003csub\u003es\u003c/sub\u003e are the absorbance of the supernatants with the treatment with the hydrogel, PBS solution, and deionized water, respectively.\u003c/p\u003e \u003cp\u003eTo evaluate the in vivo histocompatibility of the hydrogel, the rats were used as control and HBE samples. The HBE material was attached to the dorsum of the experimental group rats, and the skin reactions were monitored for 3 and 12 hours. After the removal of the material, a comprehensive examination was conducted utilizing hematoxylin and eosin (H\u0026amp;E), and Masson staining techniques to investigate the skin tissue and discern the inflammatory responses.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eEEG, MRI, and CT\u003c/h2\u003e \u003cp\u003eEEG signals were collected by a 32-channel system with the international 10\u0026ndash;20 lead method and CPz was designated as the reference. The EEG signals were recorded using the eegoTM mylab (ANT Neuro, Enschede, Netherlands) at a sampling frequency of 1500 Hz. Both the reference and working electrodes employed in testing were the HBE hydrogel specifically developed in this study. The contact impedance between brain electrode and scalp was observed in real time during EEG signal detection (Fig. \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e, Supporting Information). MRI images and CT images of the subject, both with and without the HBE, were recorded using a clinical 3.0T-SIGNA\u0026trade; Pioneer-70cm scanner (GE Healthcare, USA), and Brilliance CT Big Bore CT scanner (Philips, Netherlands).\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the funding support from the National Natural Science Foundation of China (62204210, 62071463), the National Natural Science Foundation for Distinguished Young Scholars of China (62125112), the Natural Science Foundation of Jiangsu Province (BK20220284), and XJTLU Research Development Funding (RDF-21-01-027), Zhejiang Provincial Natural Science Foundation of China (LTGY24B050001) and Ningbo Natural Science Foundation (2022J252).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315046, P.\u0026nbsp;R.\u0026nbsp;China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuoqiang Ren, Liping Zhuang, Shunying Zhao, Jinxiu Guo, Zhaoxiang Peng, Jiangfan\u0026nbsp;Lian, Botao Liu, Jingyun\u0026nbsp;Ma, Xiaodong Hu, Zhewei Zhang and Mingming Hao\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSchool of CHIPS, XJTLU Entrepreneur College (Taicang), Xi\u0026rsquo;an Jiaotong-Liverpool University, Taicang, Suzhou, Jiangsu 215400, China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQifeng Lu, Mingxuan Zhang and Yinchao Zhao\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ei\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-lab, Key Laboratory of Multifunctional Nanomaterials and Smart Systems, Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences\u0026nbsp;(CAS), 398 Ruoshui Road, Suzhou, Jiangsu 215123, P. R. China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLianhui Li and Ting Zhang\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eM. H. and T. Z designed the project. R. G. and M. H. carried out the experiments. M. Z., L. Z., L. L., J. G., B. L., J. M., X. H., Z. Z., Y. X., and F. S. carried out the experiments discussed the methodology. S. Z., Z. P. and J. L. analyze the data. R. G., M. H., and Q. L. drafted the paper. Q. L., T. Z. and M. H. supervised the project. All the author reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProf. Ting Zhang is an Editor for the Journal, no other author has reported any competing interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval and informed consent were obtained from all participants, and the protocol was approved by the Affiliated Lihuili Hospital of Ningbo University (KY2023SL036-02) and Ningbo University (12312). The study was carried out under the Helsinki Declaration.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDenny, J. C. \u0026amp; Collins, F. S. Precision medicine in 2030-seven ways to transform healthcare. Cell. 184, 1415\u0026ndash;1419 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteinmetz, J. \u003cem\u003eet al.\u003c/em\u003e Steinmetz J D, Seeher K M, Schiess N, et al. Global, regional, and national burden of disorders affecting the nervous system, 1990\u0026ndash;2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 23, 344\u0026ndash;381 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa, Q. \u003cem\u003eet al.\u003c/em\u003e Temporal trend and attributable risk factors of stroke burden in China, 1990\u0026ndash;2019: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 6, e897-e906 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, J. \u003cem\u003eet al.\u003c/em\u003e Flexible Electrodes for Brain\u0026ndash;Computer Interface System. Advanced Materials. 35, 2211012 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa, J. \u003cem\u003eet al.\u003c/em\u003e Hydrogel sensors for biomedical electronics. Chemical Engineering Journal. 481, 148317 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin, S. \u003cem\u003eet al.\u003c/em\u003e Advanced Electrode Technologies for Noninvasive Brain\u0026ndash;Computer Interfaces. ACS Nano. 17, 24487\u0026ndash;24513 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eV\u0026aacute;zquez-Guardado, A., Yang, Y., Bandodkar, A. J. \u0026amp; Rogers, J. A. Recent advances in neurotechnologies with broad potential for neuroscience research. Nature Neuroscience. 23, 1522\u0026ndash;1536 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang, M., Tang, Z., Liu, X. \u0026amp; Van der Spiegel, J. Electronic neural interfaces. Nature Electronics. 3, 191\u0026ndash;200 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang, X., Shen, H., Zhao, S., Li, N. \u0026amp; Liu, J. Flexible brain\u0026ndash;computer interfaces. Nature Electronics. 6, 109\u0026ndash;118 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYuk, H., Lu, B. \u0026amp; Zhao, X. Hydrogel bioelectronics. Chemical Society Reviews. 48, 1642\u0026ndash;1667 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark, B. \u003cem\u003eet al.\u003c/em\u003e Cuticular pad\u0026ndash;inspired selective frequency damper for nearly dynamic noise\u0026ndash;free bioelectronics. Science. 376, 624\u0026ndash;629 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXue, H. \u003cem\u003eet al.\u003c/em\u003e Hydrogel electrodes with conductive and substrate-adhesive layers for noninvasive long-term EEG acquisition. Microsystems \u0026amp; Nanoengineering. 9, 79 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu, J. \u003cem\u003eet al.\u003c/em\u003e Ten-hour stable noninvasive brain-computer interface realized by semidry hydrogel-based electrodes. Research. (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, X. \u003cem\u003eet al.\u003c/em\u003e Bioadhesive and conductive hydrogel-integrated brain-machine interfaces for conformal and immune-evasive contact with brain tissue. Matter. 5, 1204\u0026ndash;1223 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu, Y. \u003cem\u003eet al.\u003c/em\u003e Body temperature enhanced adhesive, antibacterial, and recyclable ionic hydrogel for epidermal electrophysiological monitoring. Advanced Healthcare Materials. 11, 2200653 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang, G. \u003cem\u003eet al.\u003c/em\u003e Adhesive and hydrophobic bilayer hydrogel enabled on-skin biosensors for high‐fidelity classification of human emotion. Advanced Functional Materials. 32, 2200457 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTringides, C. M. \u003cem\u003eet al.\u003c/em\u003e Viscoelastic surface electrode arrays to interface with viscoelastic tissues. Nature nanotechnology. 16, 1019\u0026ndash;1029 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei, W. \u003cem\u003eet al.\u003c/em\u003e In situ multimodal transparent electrophysiological hydrogel for in vivo miniature two-photon neuroimaging and electrocorticogram analysis. Acta biomaterialia. 152, 86\u0026ndash;99 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYuk, H., Zhang, T., Lin, S., Parada, G. A. \u0026amp; Zhao, X. Tough bonding of hydrogels to diverse non-porous surfaces. Nature materials. 15, 190\u0026ndash;196 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo, J. \u003cem\u003eet al.\u003c/em\u003e MXene-enabled self-adaptive hydrogel interface for active electroencephalogram interactions. ACS nano. 16, 19373\u0026ndash;19384 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLyu, C. \u003cem\u003eet al.\u003c/em\u003e Bone-inspired (GNEC/HAPAAm) hydrogel with fatigue-resistance for use in underwater robots and highly piezoresistive sensors. Microsystems \u0026amp; Nanoengineering. 9, 99 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHao, M. \u003cem\u003eet al.\u003c/em\u003e Tough engineering hydrogels based on swelling\u0026ndash;freeze\u0026ndash;thaw method for artificial cartilage. ACS Applied Materials \u0026amp; Interfaces. 14, 25093\u0026ndash;25103 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShin, Y. \u003cem\u003eet al.\u003c/em\u003e Low-impedance tissue-device interface using homogeneously conductive hydrogels chemically bonded to stretchable bioelectronics. Science Advances. 10, eadi7724 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang, D. \u003cem\u003eet al.\u003c/em\u003e Stretchable and durable HD-sEMG electrodes for accurate recognition of swallowing activities on complex epidermal surfaces. Microsystems \u0026amp; Nanoengineering. 9, 115 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang, J. \u003cem\u003eet al.\u003c/em\u003e Engineering electrodes with robust conducting hydrogel coating for neural recording and modulation. Advanced Materials. 35, 2209324 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang, H. \u003cem\u003eet al.\u003c/em\u003e Multifunctional Conductive Hydrogel Interface for Bioelectronic Recording and Stimulation. Advanced Healthcare Materials. 2400562 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, C. \u003cem\u003eet al.\u003c/em\u003e On-skin paintable biogel for long-term high-fidelity electroencephalogram recording. Science Advances. 8, eabo1396 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWon, D. \u003cem\u003eet al.\u003c/em\u003e Laser-induced wet stability and adhesion of pure conducting polymer hydrogels. Nature Electronics. (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan, Q. \u003cem\u003eet al.\u003c/em\u003e Hydrogel Nanoarchitectonics of a Flexible and Self-Adhesive Electrode for Long‐Term Wireless Electroencephalogram Recording and High‐Accuracy Sustained Attention Evaluation. Advanced Materials. 35, 2209606 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, X. \u003cem\u003eet al.\u003c/em\u003e Subdural neural interfaces for long-term electrical recording, optical microscopy and magnetic resonance imaging. Biomaterials. 281, 121352 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen, Z. \u003cem\u003eet al.\u003c/em\u003e Multimodal optoacoustic imaging: methods and contrast materials. Chemical Society Reviews. 53, 6068 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDucharme, S. Brain MRI research in neurodegenerative dementia: time to deliver on promises. Brain. 146, 4403\u0026ndash;4404 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarri\u0026egrave;re, D. \u003cem\u003eet al.\u003c/em\u003e The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization. Nature communications. 10, 1\u0026ndash;13 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShribman, S. \u003cem\u003eet al.\u003c/em\u003e Neuroimaging correlates of brain injury in Wilson\u0026rsquo;s disease: a multimodal, whole-brain MRI study. Brain. 145, 263\u0026ndash;275 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTian, L. \u003cem\u003eet al.\u003c/em\u003e Large-area MRI-compatible epidermal electronic interfaces for prosthetic control and cognitive monitoring. Nature biomedical engineering. 3, 194\u0026ndash;205 (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"microsystems-and-nanoengineering","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"micronano","sideBox":"Learn more about [Microsystems \u0026 Nanoengineering](http://www.nature.com/micronano/)","snPcode":"41378","submissionUrl":"https://mts-micronano.nature.com/","title":"Microsystems \u0026 Nanoengineering","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4657809/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4657809/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe exploration of the multi-dimensional brain activity with high temporal resolution and spatial resolution is of great significance in the diagnosis of neurological disease and the study of brain science. Although the integration of EEG with magnetic resonance imaging (MRI) and computed tomography (CT) provides a potential solution to achieve the brain-functional image with high spatiotemporal resolution, the critical issues of interface stability and magnetic compatibility remain challenges. Therefore, in this research, we proposed a conductive hydrogel EEG electrode with an asymmetrical bilayer structure, which shows the potential to overcome the challenges. Benefited from the bilayer structure with different moduli, the hydrogel electrode exhibits high biological and mechanical compatibility with the heterogeneous brain-electrode interface. As a result, the impedance can be reduced compared with conventional metal electrodes. In addition, the hydrogel-based ionic conductive electrodes, which are free from metal conductors, are compatible with MRI and CT. Therefore, it can obtain high spatiotemporal resolution multi-dimensional brain information in clinical settings. The research outcome provides a new approach for establishing a platform for early diagnosis of brain diseases and the study of brain science.\u003c/p\u003e","manuscriptTitle":"MRI and CT Compatible Asymmetric Bilayer Hydrogel Electrodes for EEG-Based Brain Activity Monitoring","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-09 21:37:04","doi":"10.21203/rs.3.rs-4657809/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-08-01T02:19:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-07-28T00:54:33+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-07-16T14:53:49+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-07-16T07:19:19+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-07-15T11:07:19+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-07-10T13:11:32+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-07-10T10:07:54+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-07-10T10:02:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-01T06:18:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Microsystems \u0026 Nanoengineering","date":"2024-07-01T04:28:48+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2024-07-01T02:16:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-29T06:21:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"microsystems-and-nanoengineering","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"micronano","sideBox":"Learn more about [Microsystems \u0026 Nanoengineering](http://www.nature.com/micronano/)","snPcode":"41378","submissionUrl":"https://mts-micronano.nature.com/","title":"Microsystems \u0026 Nanoengineering","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8d996de6-0f82-4073-bf78-b8dea8212c75","owner":[],"postedDate":"August 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":34391554,"name":"Physical sciences/Materials science"},{"id":34391555,"name":"Physical sciences/Engineering"}],"tags":[],"updatedAt":"2024-09-10T02:50:32+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-09 21:37:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4657809","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4657809","identity":"rs-4657809","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}