Synergy of a Complimentary Ionic Biogel Network for Through-Hair Neurohaptics

Synergy of a Complimentary Ionic Biogel Network for Through-Hair Neurohaptics | 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 Synergy of a Complimentary Ionic Biogel Network for Through-Hair Neurohaptics Huanyu Cheng, Ankan Dutta, Md Abu Sayeed Biswas, Long Meng, Ethan Gerhard, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5829714/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Understanding the neural mechanisms underlying haptic sensations is crucial for advancing neuroprosthetics. However, achieving on-site amplification non-invasively through-hair neural recordings remains a significant challenge as it requires thermoreversible, bioadhesive, and semiconducting characteristics in the same material. Typical polymer composite compromises on complementary properties. To address this, we present a membraneless organelles - inspired ionic biogel that leverages liquid–liquid phase separation. This enables a unique synergy of complementary properties, including rapid thermoreversible transitions, p-type semiconductivity, thermoelectricity, enhanced electrochemical stability, self-healing, and bioadhesive capabilities. These characteristics enable to analyze the frequency dependence of event-related desynchronization during electrical stimulation over days mimicking the frequency response of mechanoreceptors sensation. This thermoresponsive, semiconducting ionic biogel also enables a phase-reversible, self-balancing, tip-shaped vertical organic electrochemical transistor with a high transconductance of 44 mS at 40°C. The ionic biogel demonstrates synergistic complementary properties to understand through-hair neurohaptics. Physical sciences/Materials science/Soft materials/Gels and hydrogels Physical sciences/Engineering/Biomedical engineering Physical sciences/Materials science/Materials for devices/Sensors and biosensors Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Transformative advancements in the field of neuroprosthetics offer hope to amputees and individuals with severe motor impairments by potentially restoring intuitive control and even sensation in prosthetic limbs 1 . Beyond motor control, transcutaneous electrical stimulation of peripheral nerves such as median and ulnar nerves has opened new possibilities to provide haptic feedback and enable amputees to experience projected touch sensations in their missing limbs 2 , 3 . However, current evaluations of these sensations often rely on subjective self-reports, limiting the precision and repeatability that are essential to further optimize prosthetic design 2 . Neurohaptics provides an objective measure of neural responses to sensory stimulation to enable refined, effective haptic feedback, which can seamlessly integrate neuroprosthetics with the user's sensory perceptions 4 , 5 . The potential applications of neurohaptics also extend beyond prosthetics into the realm of augmented reality (AR) and virtual reality (VR), where sensory feedback could create immersive, interactive source-effector haptic experiences—presenting a highly promising commercializable approach 6 . This approach leverages projected sensations, enabling a seamless, comfortable AR/VR experience without compromising user immersion. Yet, as with neuroprosthetics, the field lacks consistent, objective data on neural responses to such haptic feedback, relying predominantly on subjective reports that limit the potential for standardization and optimization. Understanding the neural mechanisms of haptic feedback during transcutaneous electrical nerve stimulation (TENS) holds promise to further advance the developments of neurohaptics. Event-related desynchronization (ERD) in the alpha or beta frequency band of electroencephalography (EEG) is a well-established biomarker of sensorimotor processing, frequently observed during tactile and mechanical stimuli such as vibration or pressure 7 – 9 . However, it remains unclear whether similar ERD responses are elicited through TENS, bypassing mechanoreceptors and directly activates sensory nerves. Identifying ERD in response to TENS would indicate that the sensorimotor cortex interprets these impulses as tactile inputs, providing an objective marker for tracking neural engagement and response fidelity in haptic interfaces. Moreover, long-term TENS invokes neuroplastic mechanisms that dynamically shape sensory perception over time 10 , 11 . Initially, repeated stimulation can intensify perceived sensations, potentially due to synaptic strengthening and recruitment of additional neural pathways 12 . However, with continued use, these sensations often diminish, reflecting neural habituation and circuit reorganization. This adaptation underscores the need for dynamic feedback systems that adjust stimulation to counteract habituation and sustain effective sensory feedback. Despite this potential, current approaches lack objective metrics for real-time monitoring of neural responses to haptic stimulation, and materials suitable for stable, long-term, and high-fidelity TENS and through-hair EEG recordings that could capture such responses. To address the persistent challenges in neurohaptics research of obtaining objective non-invasive EEG neural recording over the hair-covered motor cortex area (e.g. C3, C4, Cz) during haptic sensation, we introduce an ionic biogel network system with thermoresponsive and semiconducting characteristics, capable of concurrent high-fidelity, long-term through-hair neural recording and TENS ( Fig. 1 a ) . The ionic biogel synergistically combines two material systems with independent yet complementary bonding mechanisms to result in a softer material with faster sol-gel transitions and enhanced mechanical, electrical, and electrochemical properties (Extended Fig. 1 a ) . In particular, the electrostatic interactions between the poly(3,4-ethylenedioxythiophene) poly(styrene sulfonate) (PEDOT:PSS) and a plasticizer such as ionic liquid, here 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM-TFSI) (ionic system) 13 are combined with the hydrogen-bonding network of the gelatin-glycerol-salt hydrogel matrix (biogel system) 14 . The resulting ionic biogel addresses the challenges associated with through-hair EEG and TENS in three key aspects. First, its thermoresponsive properties (from the biogel system) provide the ionic biogel with the rapid gel-sol transition to conform to the scalp/skin upon gentle heating, thus maintaining stable, robust contact for reliable neural recording and haptic stimulation. Second, the viscoelastic flow behaviour (from the biogel system) of the ionic biogel maximizes the contact area to reduce the skin contact impedance and improve signal-to-noise ratios even upon motions due to the bioadhesive properties. Although the thermoresponsive behavior of a biogel-based system has been previously demonstrated for through-hair EEG recording, prior material systems do not possess the rapid thermoreversibility, high water retention, and electrochemical stability necessary for sustained operation over days to weeks 14 , 15 . Third, leveraging the semiconducting properties of PEDOT:PSS (from ionic system) 16 – 19 , the ionic biogel can function as a thermoreversible p-type semiconductor to enable the integration of the organic electrochemical transistors (OECTs) as through-hair active electrodes with on-site amplification. Previously, OECTs have been employed for high-fidelity neural recordings 20 , 21 , but they lack thermoreversible and bioadhesive characteristics to enable a robust, through-hair EEG recording. Collectively, the unified properties of this ionic biogel enable the synthesis of bioadhesive semiconducting hydrogel-based interfaces exhibiting rapid gel-sol transitions—providing stable, high-quality, long-term through-hair EEG recordings and haptic stimulation. Typical polymer blending often yields a mere averaged combination of favourable properties, rather than achieving true functional synergy. In contrast, harnessing the synergy inherent in complementary material systems requires capitalizing on the spatial and compositional segregation characteristic of liquid–liquid phase separation (LLPS) 22 – 25 . Membraneless organelles (MLOs) in biological cells exemplify this principle: by partitioning biomolecules into distinct coexisting phases, MLOs leverage metastability and rapid, reversible transitions to integrate and optimize diverse functionalities 26 , 27 . Drawing inspiration from nature’s optimized LLPS-driven functionality of MLOs, the design of phase-separated ionic biogels strategically fuses dissimilar but complementary phases to realize synergy. One phase, formed from the PEDOT:PSS/EMIM-TFSI system, imparts high ionic conductivity, p-type semiconducting behavior, thermoelectricity, robust water-retention characteristics, and high electrochemical stability, enabling long-term, high-fidelity neural recording, and precise electrical stimulation. The other phase, the biopolymeric gelatin–glycerol–salt matrix, introduces biocompatibility, bioadhesive properties, self-healing capabilities, and thermoresponsive behaviour, and also contributes to the thermopower. Together, these coexisting phases maintain a phase-separated metastable state that allows for rapid, thermoreversible sol-gel transitions, facilitating conformality. This synergy yields an MLO-inspired, phase-separated ionic biogel with a unified combination of properties—metastability, thermoreversibility, porosity, p-type semiconductivity, high air permeability, long-term stability, injectability, and strain insensitivity. Characterisation of the synergistic ionic biogel network The complementary properties of the ionic biogel stem from the synergistic interplay of phase-separated PEDOT:PSS/EMIM-TFSI ionic system and the gelatin-glycerol-salt hydrogel matrix (Extended Fig. 1 b ) . The independence of these two material systems (Supplementary Note 1) minimizes unfavourable inter-network interactions, as their primary bonding mechanisms—electrostatic interactions (in ionic system) and hydrogen bonds (in biogel system)—operate within distinct individual phases. This arrangement exhibits metastability and phase separation, typically observed in MLOs, where compartmentalization arises from weak, dynamic interactions 24 , 26 (Supplementary Note 2) . Initially, the mixture forms an amorphous state due to kinetic constraints and limited molecular mobility at room temperature; upon heating, increased chain mobility reduces the Gibbs free energy of mixing ( \(\:\varDelta\:{G}_{mix}\) ), leading to partial miscibility 28 . Upon cooling, the spatial separation (Figure S1 ) and difference in energy scales elevate the Gibbs free energy of mixing \(\:\varDelta\:{G}_{mix}\) , favouring phase separation and the formation of a metastable MLO-inspired composite material (Supplementary Note 3) . The stable open electrochemical potential of -40 mV for > 7 hours (Figure S2) indicates that the interface does not spontaneously homogenize because that would require overcoming significant energy barriers: interfacial tension, rearrangement of polymer chains, re-solvation or displacement of ions, and possibly changes in polymer redox states 29 (Supplementary Note 4) . The molecular interactions between the gelatin-glycerol-salt hydrogel matrix and the PEDOT:PSS/EMIM-TFSI ionic system can be elucidated from a comprehensive series of characterizations (Supplementary Note 5, Figures S3-S8, Extended Figs. 2 a- 2 f ) . Results and Discussion One of the essential characteristics of the ionic biogel is a sharper gel-sol transition at ~ 40°C to ensure rapid extrusion of the material onto the scalp. Metastability, akin to the behaviour observed in MLOs, can be experimentally validated through rapid phase transitions captured in rheological measurements 26 . The storage modulus of the ionic biogel composite transitions from 7 kPa at room temperature to 3.4 kPa at scalp temperature (35°C) and then to a very low modulus of 60 Pa at 45°C ( Fig. 2 a ) . This transition facilitates mechanical adaptability to flow and exert minimal strain on the scalp and surrounding hair, compared to normal biogel 14 , 15 (Supplementary Note 6, Figures S9-S10, Extended Figs. 3 a- 3 b ) , following a the modified-Ellis equation for the temperature-sweep rheology (Supplementary Note 7) . A cyclic thermal ramping protocol is employed to investigate the material's ability to recover its initial rheological characteristics ( Fig. 2 b ) , demonstrating its metastable characteristics (Supplementary Note 8, Figures S11-S16, Extended Fig. 3 c ) , which can be modelled as a spring-damper model with different growth time constants to account for decay and reversibility (Supplementary Note 9) . The ionic biogel has distinct mechanical and adhesive properties in shear and normal direction (Supplementary Note 10, Figures S17-S19, Extended Fig. 3 d ) . The ionic biogel shows high water retention property (~ 97% at 70°C) ( Fig. 2 c ) and water vapour transmission rate (~ 1417 g/m 2 /day) (Supplementary Note 11, Figure S20, Extended Fig. 3 e ) . The synergistic interaction of thermodiffusion and thermogalvanic effects 30 in ionic biogel composite drives a high Seeback coefficient of 21 mV/K (till 3 K change) and then 4 mV/K (till 8 K change), offering promising application opportunities in low-grade thermal energy harvesting and wearable thermoelectric devices (Supplementary Note 12, Extended Fig. 3 f ) . The porous nature of the ionic biogel from phase separation along with the electrostatic interaction of PEDOT:PSS/ionic liquid makes it much softer than the normal biogel (Supplementary Note 13, Figures S21, S22) . One of the most important benefits of phase-separation is the strain-insensitivity of the ionic biogel which only increases its resistance by 100% after reaching its strain limit of 380%, which represents the record high strain insensitivity among all types of hydrogels to our knowledge 31 – 36 ( Figs. 2 d, S23 ) . The material shows noticeable changes (> 1%) in resistance only after > 30% strain. The material also shows negligible hysteresis with resistance returning to its original value with only a 1% change. The performance of the through-hair electrophysiology hinges on the skin contact impedance through the hair (Supplementary Note 14, Figures S24-S29, Extended Figs. 4 a- 4 d ) , where the impedance of 1.5 kΩ (diameter ~ 2 cm) from the ionic biogel at 4 kHz is more than three orders of magnitude smaller than that of 4.4 MΩ from the commercial Ag/AgCl electrode ( Fig. 2 e ) . The low skin-contact impedance shows a robust EMG signal during flexing (Supplementary Note 15, Figures S30-S34) . Charge injection capacity (CIC) is one of the most crucial parameters for evaluating the performance of electrical stimulation in neuroprosthetics 31 , 37 , 38 . The CIC of the ionic biogel is 10 mC/cm² at 33 Hz and 5 mC/cm² at 67 Hz ( Fig. 2 f ) , which are comparable to existing materials used for similar applications 31 , 38 (Supplementary Note 16, Figures S35-S40, Extended Figs. 4 e- 4 f ) . The thermoresponsive and conducting properties of the ionic biogel ensure stable, high-quality, long-term signal acquisition and reliable stimulation, even with different hair types or skin oils. An increase in EEG power amplitude during closed eyes state is observed with ( Fig. 3 a ) and without sweat (Figure S41) compared to open eyes state. The efficacy of the ionic biogel electrode is demonstrated through ERD in the recording of neural responses associated with motor cortex activity during mechanical or natural sensation (Supplementary Note 17, Figures S42-S46, Extended Figs. 5a-5e) . The EEG power spectrum at C3 and Cz during sensory mechanical vibration (using a vortex vibrator) reveals a similar ERD trend: a reduction in beta power amplitude at Cz during weight repetitions, but no ERD reflected at C3 9 ( Fig. 3 b, Extended Fig. 5f) . ERD has been known to occur during hand or finger movement 7 , 8 , which is also consistent with mechanical vibration. However, to the best of our knowledge, no prior studies have correlated ERD with haptic sensations induced by TENS of the ulnar nerve. In this context, neural responses during cutaneous electrical stimulation are evaluated with a wearable stimulator array (Extended Fig. 6) consisting of an 8×2 grid of electrodes arranged with a constant pitch of 1.5 cm to cover the right arm (Supplementary Note 18, Figure S47) . On Day 1, the perceived force sensation is increased from 0.07 N to 0.5 N as the stimulation current applied to the ulnar nerve is increased from 3.1 mA to 3.9 mA, till the subject reports perceived pain (pain threshold) ( Fig. 3 c ) . Notably, on Day 2, the baseline force perception at the same stimulation current of 3.1 mA increases to 0.3 N, suggesting a possible sensitization or adaptation effect within the nervous system. A decrease in the pain threshold (current amplitude at which the pain onsets) is observed on Days 4 and 7, with similar force sensations of ~ 0.1 N being elicited at a significantly lower stimulation current of 2 mA. Specifically, on Day 4, a stimulation current of 3 mA can induce a sensation force that is about 842% of the value induced by the 3.1 mA stimulation on Day 1. Although the sensation force on Day 4 exhibits a similar trend and range to that observed on Day 7, there is a slight increase of ~ 20% at 3 mA (the higher end of the current range). These findings indicate potential neuroplastic changes occurring over repeated stimulation sessions, possibly involving peripheral sensitization mechanisms that enhance neural responsiveness to electrical stimuli 10 , 11 . A significant challenge in EEG recordings during simultaneous electrical stimulation is the introduced artifacts, particularly charging artifacts resulting from current flow through the body, which can produce high-amplitude voltages (tens of millivolts range) at the scalp and contaminate the EEG signal (in microvolts range). By positioning the ground electrode along the cervical region and ulnar nerve pathway rather than behind the ear, these artifacts are reduced from approximately 40 mV to 4 mV. The artifacts are further reduced by sequential post-processing methods such as empirical mode decomposition (EMD) 39 , bandpass/notch filters, and downsampling (Supplementary Note 19) . The artifact removal is generally performed using Independent Component Analysis (ICA) 40 that leverages the statistical independence of multiple channels. However, as the number of electrodes is two in this work, ICA’s performance is restricted. Therefore, EMD is utilized to decompose the signal into several intrinsic mode functions (IMFs) with the first mode corresponding to the stimulation artifacts. Similar to mechanical stimulation, ERD is also observed during electrical stimulation, which is marked by a reduction of power in alpha-wave, averaged across trials for all amplitudes ( Fig. 3 d ) . Different frequency (5-500 Hz) of electrical stimulation (of amplitude of 3.7 mA) is elicited to record the change of alpha power in EEG during stimulation ( Fig. 3 e, Supplementary Note 20) . The neural response (alpha power of EEG) across different frequencies increases, reaching a maximum at 50 Hz and also around 500 Hz, corresponding to the resonant frequencies of mechanoreceptors such as Meissner Corpuscles and Pacinian corpuscles 2 , 41 , 42 respectively, as shown in other methods during mechanical/natural stimulation (Supplementary Note 21) . This power attenuation (Figure S48) and its spectrum across different frequencies persist on Day 7 ( Fig. 3 f ) . Designing through-hair active electrodes with low skin contact impedance necessitates navigating several interdependent constraints, especially when utilizing thermoresponsive, semiconducting materials that undergo gel-sol phase transitions. The multiphysics nature of the problem arises from the interplay between thermal dynamics, phase transitions, fluid mechanics, solid mechanics, and transistor physics. Notably, the viscosity of the ionic biogel depends on temperature, influencing fluid flow and ion transport within the ionic biogel domain. To simplify without the loss of generality, we focus on optimizing a tip-shaped neural interface, where the tip diameter corresponds to the channel length \(\:L\) between the source and drain of a vertical OECT ( Fig. 4 a ) . In the vertical OECT localized at the tip with gold source/drain electrodes, the column is filled with a thermally conductive graphite-PDMS composite to enhance thermal transport, actively regulated by a Peltier module atop the assembly. The channel length or the diameter of the tip can be optimized as around 2.8 mm, for a 1 cm long tip which self-balances itself (Supplementary Note 22, Figure S49) , also confirmed from COMSOL Multiphysics simulation (Supplementary Note 23, Extended Figs. 7a-7c) . The electrical impedance and capacitance of the tip-shaped OECT are measured to be approximately 120 Ω and 40 µF at 100 Hz and room temperature, respectively (Supplementary Note 24, Figure S50) . The decrease in the skin contact impedance improves the signal coupling (Supplementary Note 25) . The transconductance of the OECT exhibits a strong dependence on temperature and the choice of electrolyte. Phosphate-buffered saline (PBS), a conventional electrolyte for OECTs, tends to dehydrate at elevated temperatures, impairing ionic conductivity and device performance. To address this limitation, the ionic liquid EMIM-TFSI is employed as the electrolyte due to its high thermal stability and excellent ionic conductivity. At a drain voltage of 0.2 V, the OECT displays a maximum transconductance of 7.8 mS at 20°C. This transconductance increases to 35 mS at 30°C and further to 44 mS at 40°C ( Fig. 4 b ) . The enhancement in transconductance with temperature can be attributed to several factors, including increased ionic mobility, thermoresponsive gelatin-glycerol matrix (decreased viscosity at higher temperatures to allow for more rapid ion diffusion and improved coupling between the gate and channel), and enhanced electronic conductivity (from increased chain mobility and enhanced π–π stacking interactions). However, upon surpassing the phase transition temperature of the gelatin-glycerol matrix at approximately 42°C, the transconductance is dramatically decreased to 0.3 mS at 50°C. This sharp decline is attributed to the loss of structural integrity of the hydrogel matrix as it transitions from a gel to a sol state, causing the ionic biogel to flow. The phase transition can be avoided by operating below the phase-transition temperature, enabling phase-reversible OECTs (Figure S51) . Notably, at a negative drain voltage of − 0.4 V, the transconductance remains low (< 3 mS) across the entire temperature range. This asymmetry in device behaviour suggests that the OECT is more efficient in modulating channel current through hole depletion rather than accumulation, consistent with the p-type semiconducting nature of PEDOT:PSS. A similar trend is observed when PBS is used as the electrolyte ( Figs. 4 c, 4 d ) , although the overall performance is inferior compared to EMIM-TFSI. The dehydration of PBS at higher temperatures reduces ionic conductivity and impairs the gating efficiency, leading to lower transconductance values. This comparison highlights the critical role of the ionic liquid EMIM-TFSI in maintaining high ionic conductivity and thermal stability, essential for the OECT's operation at elevated temperatures. Conclusion Looking ahead, this work sets a foundation for further exploration into complementary material systems to develop next-generation neurointerfaces with enhanced functionality. By leveraging synergistic interactions, such as those provided by the combination of the hydrogen-bonded gelatin matrix with the PEDOT:PSS/ionic liquid domains, designs can further tune properties such as ionic conductivity, charge retention, mechanical adaptability, and durability to specific neurophysiological needs. The introduction of phase-separated, porous architectures within these materials could further augment their electrochemical performance, enabling seamless transitions between ionic and electronic conductivity within a three-dimensional, volumetric framework. Such advancements are expected to drive significant progress in the emerging field of neurohaptics, where finely-tuned materials can bridge the gap between sensory feedback and neural stimulation, offering users immersive and responsive experiences. By creating adaptive, responsive materials that closely mimic biological tissues, we are better positioned to study sensory processing, adaptation, and long-term neural plasticity. This work underscores the transformative potential of bioinspired, multifunctional materials in enabling new frontiers in neural engineering, paving the way for neuroprosthetics and wearable neurotechnologies that seamlessly integrate with human physiology. Methods XPS XPS experiments were performed using a Physical Electronics VersaProbe III instrument equipped with a monochromatic Al kα x-ray source (hν = 1,486.6 eV) and a concentric hemispherical analyzer. Charge neutralization was performed using both low-energy electrons (< 5 eV) and argon ions. The binding energy axis was calibrated using sputter cleaned Cu (Cu 2p3/2 = 932.62 eV, Cu 3p3/2 = 75.1 eV) and Au foils (Au 4f7/2 = 83.96 eV). 43 Peaks were charge referenced to the CHx band in the carbon 1s spectrum at 284.8 eV. Measurements were made at a takeoff angle of 45° with respect to the sample surface plane. This resulted in a typical sampling depth of 3–6 nm (95% of the signal originated from this depth or shallower). Quantification was done using instrumental relative sensitivity factors (RSFs) that account for the x-ray cross-section and inelastic mean free path of the electrons. On homogeneous samples major elements (> 5 atom%) tend to have standard deviations of < 3% while minor elements can be significantly higher. The analysis size was ~ 200 µm in diameter. Raman Spectroscopy Raman spectroscopy was employed to investigate the surface composition and structural properties of the composite using a Horiba LabRAM HR Evolution confocal microscope equipped with a 785 nm laser and a 300 g/mm grating. The characterization was conducted across various temperatures to assess temperature-dependent changes. FTIR FTIR measurements were conducted using a Bruker V70 spectrometer (wavenumber range: 4000 to 600 cm⁻¹, resolution: 6 s⁻¹) to examine the chemical bonding and identify organic and inorganic components in the modified nanocomposite films through infrared light. The characterization was performed at different temperatures to evaluate temperature-dependent changes. Biocompatibility Test Hydrogel samples were cut into circular films with 10 mm diameter and added to PBS to prepare hydrogel extracts, and 1.0 mL of the extract was put into a 24-well plate for UV irradiation. For each well containing hydrogel extract, 2×10 4 MCF-10A was added and the proliferation medium was supplemented to 1.0 mL. For the wells without material, 2×10 4 MCF-10A was also added and the proliferation medium was supplemented to 1.0 mL as the control group. The 24-well plate containing MCF-10A and the extract was incubated in a cell culture incubator, and 200 µL of proliferation medium was added to each well every two days. The proliferation of MCF-10A on the hydrogel extract on days 1 and 2 after co-culture was determined using MTT. After adding the FDA, the staining results were observed using a fluorescence microscope. Mechanical Testing General Procedures All mechanical and adhesive testing was conducted on an Instron J5966 testing frame (Instron, Binghamton, NY, USA) with a 1 kN load cell and utilizing Bluehill Universal mechanical testing software (Instron). Compression Testing Compression testing between parallel plates (Instron) was carried out on hydrogel specimens with a diameter of 8 mm and thickness of 1 mm to 90% strain at a strain rate of 1.3 mm/min. Initial modulus and peak stress at 90% strain were calculated from the stress profile over the initial 10% strain and the maximum stress value, respectively. Tensile Testing : Tensile testing was carried out using pneumatic grips (Instron) on hydrogel samples (length × width × thickness: 3 cm × 1 cm × 1mm) at a strain rate of 50 mm/min. Initial tensile modulus, peak stress, and peak strain were calculated from the stress profile over the initial 10% of strain and the maximum stress and strain values, respectively. Adhesive Testing Lap shear adhesive testing was carried out using pneumatic tensile grips. Strips of porcine tissue (1 cm width) were adhered in a lap configuration with an adhesive area of 1 cm 2 and placed within the tensile grips (with the adhered region outside of the gripped area). The tensile force was then applied at a rate of 5 mm/min until adhesive failure and the maximum adhesive force was recorded. 90° adhesive peel testing was carried out by first gluing a porcine tissue strip (1 cm width) to a flat acrylic plate, which was then attached to the bottom compression plate of the mechanical testing frame using vice grips. Another strip of porcine tissue was adhered to this first piece using the appropriate hydrogel adhesive to create an adhesive area of 1 cm 2 . The other, free end of the second strip was then gripped by the top pneumatic grip of the testing frame, after which a tensile force was generated to the top to achieve the 90° peel, with adhesive force measured as above. Rheological Testing General Procedures All rheological testing was conducted on a DHR-2 rheometer (TA Instruments, New Castle, DE, USA) using TRIOS software (TA Instruments) in a 20 mm parallel plate configuration (sandblasted plate faces) with a Peltier plate to control temperature. Hydrogel samples with a diameter of 20 mm and height of 1 mm were used at 25°C unless stated otherwise. Shear Sweep Shear sweeps were first conducted to establish the linear response region from 0.01 to 1,000% strain at a frequency of 1 Hz. Frequency Sweep Frequency sweeps were conducted from 0.1 to 100 Hz within the linear response region (0.05% strain). Temperature Sweep Temperature sweeps were conducted from 25 to 60°C with a ramp rate of 1°C/min (1 Hz and 0.05% strain). Cyclical Recovery Test : Cyclic recovery tests were conducted in 3 phases: an initial ramp from 25 to 60°C at a rate of 5°C/min (1 Hz and 0.05% strain), a cooling ramp from 60 to 25°C at a rate of 5°C/min (1 Hz and 0.05% strain), and a recovery interval at 25°C for 900 s (1 Hz and 0.05% strain). The above 3 phases were repeated over successive 4 cycles. Stimulation Procedure A 26-year-old male human subject participated in the stimulation experiment. During the experiment, the subject was comfortably seated in a chair. The electrical stimuli were delivered via a set of 2×8 gel-based electrodes (Fig. 6 (b)). Each electrode with a diameter of 1 cm was replaced with the reported ionic biogel to enhance conductivity. The electrodes were positioned along the medial portion of the right upper arm, just beneath the short head of the biceps brachii, targeting the area near the median and ulnar nerves. This placement aligned with the way extending from the center of the armpit to the inner side of the elbow (medial epicondyle of the humerus), ensuring placement over the nerve pathways located below the skin. To deliver the electrical stimuli via a specific pair of electrodes (Fig. 6(b)), a custom-built MATLAB interface to control a switch matrix (Agilent Technologies, Santa Clara, CA) for electrode pair selection was used. The MATLAB interface can also configure the stimulation parameters of the stimulator (STG4008, Multichannel Systems, Reutlingen, Germany). Specifically, single biphasic rectangular pulses (Fig. 2 (a)) were delivered to selected electrodes with a pulse width of 200 µs and a stimulation frequency of 150 Hz. To indicate the force evoked by stimulation, the subject's right hand was placed on a force load cell (LCM201-100N, Newark Electronics, Chicago, IL) with a sampling frequency of 1,000 Hz, allowing the subject to apply varying levels of pressure with the index finger in response to force evoked by stimulation. 44 A grid search was initially performed to identify a pair of electrodes that could effectively induce flexion in at least one finger, while minimizing wrist movement and avoiding any discomfort. Once identified, this electrode pair was used for subsequent experiments. Multiple 3-s stimulation trials were conducted, with the pulse amplitude gradually increased until the subject reported discomfort. The measured forces during the plateau period were averaged to indicate the force evoked by stimulation. The evaluation of the long-term usability of the reported ionic biogel involved a series of experiments over the span of one week, specifically on Days 1, 2, 4, and 7. Materials Gelatin from porcine skin powder with gel strength 300 g Bloom Type A, Glycerol 99%, sodium chloride (NaCl), and the ionic liquid 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide with a concentration of 98% (HPLC) were purchased from Sigma Aldrich. PEDOT:PSS (PH 1000) in aqueous solution was purchased from Ossila. 13 – 15 For PDMS, Sylgard 184 Elastomer Base and its Curing Agent from Electron Microscopy Sciences were used at a 10:1 ratio. Preparation of Biogel Original Biogel The biogel was prepared by dissolving 0.11 grams of sodium chloride in 1 mL of water. Afterward, 0.75 grams of glycerol were added and mixed, followed by adding and thorough mixing of 0.5 grams of gelatin. 14 , 15 The solution was left for 2 hours so the gelatin could absorb all the components and then heated in an oven at 80ºC for 45 minutes. At this time, the biogel could be used as a gel with relatively liquid and highly adhesive properties. For storage or later use, the gel was left at room temperature for around 6 hours to solidify. The biogel could be heated at any time afterward to reacquire its liquid form. Ionic Biogel The ionic biogel was prepared by dissolving 0.11 grams of sodium chloride in 1 mL of PEDOT:PSS in an aqueous solution. Afterward, 1 mL of ionic liquid was added and mixed thoroughly. 13 After 5 mins, 0.75 grams of glycerol were added and mixed, followed by adding and thorough mixing of 0.5 grams gelatin. The solution was left for 2 hours so the gelatin could absorb all the components and then heated in an oven at 80ºC for 45 minutes. At this time, the ionic biogel could be used as a gel in a relatively liquid form. For storage or later use, the resulting ionic biogel was left at room temperature for around 6 hours to solidify. The ionic biogel could be heated at any time afterward to reacquire its liquid and adhesive properties. Declarations Competing Interests The authors declare no competing interests. Funding H.C. acknowledges the support provided by NIH (Award No. R21EB030140), NSF (Grant Nos. 2319139 and 2309323), and Penn State University. A.D. acknowledges the support provided by NIH Training Grant T32NS115667, Diefenderfer Graduate Fellowship in Entrepreneurship, NSF I-Corps grant (2419142), and the Leighton Riess Graduate Fellowship at Penn State University. All human subject studies were approved by The Pennsylvania State University (protocol numbers STUDY00009245 and STUDY00021035) with the informed consent obtained from the volunteers. Author Contributions Under the supervision of H.C., A.D. conceived the ideas, designed the research, synthesized the material, performed the theoretical modeling, simulations, processed the data and analysed the results. M.A.S.B. and A.M.C. optimized the material composition and prepared the electrodes, stimulating array. L.M. and X.H. developed the stimulation protocol and sensation results. A.D., E.G. and J.Y. conducted the rheological and mechanical characterization. W.Z. participated in experimental setup of thermoelectric characterization and performed UV-Vis and XPS characterization. A.M.A characterization temperature-dependent FTIR and Raman. L.J. developed electrodes. Y.C. performed biocompatibility test. A.D. and H.C. wrote the manuscript with input from all authors. Acknowledgements A.D. thanks Dr. Dipankar Bhowmik from The Pennsylvania State University, University Park for the discussion on phase-separated Membraneless Organelles. We also thank Dr. Sarah Kiemle and Dr. Nichole Wonderling from Material Research Institute, The Pennsylvania State University for AFM and WAXS characterization, respectively. References Adewole DO et al (2016) The Evolution of Neuroprosthetic Interfaces. Crit Rev Biomed Eng 44:123–152 Blau R et al (2024) Conductive block copolymer elastomers and psychophysical thresholding for accurate haptic effects. Sci Robot 9:eadk3925 Gupta A, Vardalakis N, Wagner FB (2023) Neuroprosthetics: from sensorimotor to cognitive disorders. Commun Biol 6:14 Alsuradi H, Park W, Eid M (2020) EEG-Based Neurohaptics Research: A Literature Review. IEEE Access 8:49313–49328 Park W, Kim L, Ball T, Atashzar SF, Editorial (2022) NeuroHaptics: From Human Touch to Neuroscience. Front Neurosci 16:964014 Khan Y et al (2024) On Stress: Combining Human Factors and Biosignals to Inform the Placement and Design of a Skin-like Stress Sensor. in Proceedings of the CHI Conference on Human Factors in Computing Systems 1–13 (ACM, Honolulu HI USA, 10.1145/3613904.3643473 Peter J et al (2022) Movement-related beta ERD and ERS abnormalities in neuropsychiatric disorders. Front Neurosci 16:1045715 Meirovitch Y, Harris H, Dayan E, Arieli A, Flash T (2015) Alpha and Beta Band Event-Related Desynchronization Reflects Kinematic Regularities. J Neurosci 35:1627–1637 Yakovlev L, Syrov N, Miroshnikov A, Lebedev M, Kaplan A (2023) Event-Related Desynchronization Induced by Tactile Imagery: an EEG Study. eneuro 10, ENEURO.0455-22.2023 Beijora AC, Back AP, Fréz AR, Azevedo MRB, Bertolini G (2023) R. F. Peripheral electrical stimulation on neuroplasticity and motor function in stroke patients: a systematic review and meta-analysis. Neurol Res 45:1111–1126 Meesen RLJ, Cuypers K, Rothwell JC, Swinnen SP, Levin O (2011) The effect of long-term TENS on persistent neuroplastic changes in the human cerebral cortex. Hum Brain Mapp 32:872–882 Cuypers K, Levin O, Thijs H, Swinnen SP, Meesen RL (2010) J. Long-Term TENS Treatment Improves Tactile Sensitivity in MS Patients. Neurorehabil Neural Repair 24:420–427 Wang Y et al (2017) A highly stretchable, transparent, and conductive polymer. Sci Adv 3:e1602076 Wang C et al (2022) On-skin paintable biogel for long-term high-fidelity electroencephalogram recording. Sci Adv 8:eabo1396 Lan L et al (2024) Skin-Inspired All‐Natural Biogel for Bioadhesive Interface. Adv Mater 36:2401151 Rivnay J et al (2015) High-performance transistors for bioelectronics through tuning of channel thickness. Sci Adv 1:e1400251 Khodagholy D et al (2013) High transconductance organic electrochemical transistors. Nat Commun 4:2133 Rivnay J et al (2018) Organic electrochemical transistors. Nat Rev Mater 3:17086 Rivnay J et al (2016) Structural control of mixed ionic and electronic transport in conducting polymers. Nat Commun 7:11287 Spyropoulos GD, Gelinas JN, Khodagholy D (2019) Internal ion-gated organic electrochemical transistor: A building block for integrated bioelectronics. Sci Adv 5:eaau7378 Cea C et al (2020) Enhancement-mode ion-based transistor as a comprehensive interface and real-time processing unit for in vivo electrophysiology. Nat Mater 19:679–686 Duan C, Wang RA (2024) Unified Description of Salt Effects on the Liquid–Liquid Phase Separation of Proteins. ACS Cent Sci 10:460–468 Brangwynne CP et al (2009) Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation. Science 324:1729–1732 Liu J et al (2024) Metastable biological matter in liquid phase separation. Appl Res 3:e202300071 Li L, Hou Z (2022) Theoretical modelling of liquid–liquid phase separation: from particle-based to field-based simulation. Biophys Rep 8:55–67 Hirose T, Ninomiya K, Nakagawa S, Yamazaki T (2023) A guide to membraneless organelles and their various roles in gene regulation. Nat Rev Mol Cell Biol 24:288–304 Li Y et al (2024) Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications. Signal Transduct Target Ther 9:305 Fritsch AW et al (2021) Local thermodynamics govern formation and dissolution of Caenorhabditis elegans P granule condensates. Proc. Natl. Acad. Sci. 118, e2102772118 Li X (2022) Constrictions Induced Metastability and Kinetic Stability for Advanced Solid-State Battery Design. in Encyclopedia of Energy Storage 180–190Elsevier. 10.1016/B978-0-12-819723-3.00052-4 Han C-G et al (2020) Giant thermopower of ionic gelatin near room temperature. Science 368:1091–1098 Zhou T et al (2023) 3D printable high-performance conducting polymer hydrogel for all-hydrogel bioelectronic interfaces. Nat Mater 22:895–902 Liu Y et al (2020) Morphing electronics enable neuromodulation in growing tissue. Nat Biotechnol 38:1031–1036 Wu S et al (2024) Spider-silk-inspired strong and tough hydrogel fibers with anti-freezing and water retention properties. Nat Commun 15:4441 Zhao W et al (2023) Road Narrow-Inspired Strain Concentration to Wide‐Range‐Tunable Gauge Factor of Ionic Hydrogel Strain Sensor. Adv Sci 10:2303338 Wei H et al (2021) Orthogonal photochemistry-assisted printing of 3D tough and stretchable conductive hydrogels. Nat Commun 12:2082 Zhao Y et al (2020) Hierarchically Structured Stretchable Conductive Hydrogels for High-Performance Wearable Strain Sensors and Supercapacitors. Matter 3:1196–1210 Ganji M, Tanaka A, Gilja V, Halgren E, Dayeh SA (2017) Scaling Effects on the Electrochemical Stimulation Performance of Au, Pt, and PEDOT:PSS Electrocorticography Arrays. Adv Funct Mater 27:1703019 Deng J et al (2024) A bioadhesive pacing lead for atraumatic cardiac monitoring and stimulation in rodent and porcine models. Sci Transl Med 16:eado9003 Zhuang N et al (2017) Emotion Recognition from EEG Signals Using Multidimensional Information in EMD Domain. BioMed Res. Int. 8317357 (2017) Hyvärinen A (2013) Independent component analysis: recent advances. Philos Trans R Soc Math Phys Eng Sci 371:20110534 Lipomi DJ, Dhong C, Carpenter CW, Root NB, Ramachandran VS (2020) Organic Haptics: Intersection of Materials Chemistry and Tactile Perception. Adv Funct Mater 30:1906850 Flavin MT et al (2024) Bioelastic state recovery for haptic sensory substitution. Nature 635:345–352 Seah MP (2001) Summary of ISO/TC 201 Standard: VII ISO 15472: 2001—surface chemical analysis—x-ray photoelectron spectrometers—calibration of energy scales. Surf Interface Anal 31:721–723 Shin H, Watkins Z, Huang H, Helen), Zhu Y, Hu X (2018) Evoked haptic sensations in the hand via non-invasive proximal nerve stimulation. J Neural Eng 15:046005 Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation.docx Supplementary Information ExtendedFigures.docx Cite Share Download PDF Status: Posted Version 1 posted 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-5829714","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":411353782,"identity":"06fb970f-af22-404d-85d5-9d706a63b833","order_by":0,"name":"Huanyu Cheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYBACgwMQWt4ARH6AChKlxXADkGCcQYqWBJAWZh6itNxIfvaYt40hwZy99/Br2x11iQ3szdsk8Gmxv5FmbgzSYtlzLs0698zhxAaeY2V4tRjcSDCTBmkxuJFjZpzbdiCxQSLHjICW9G8QLfffmBlbtgEdJv+GkJYciC0bbvAYP2ZsYwbawkNAy5k3ZZJzzkkYbjiTY8bYe+awcRtPWrEFXi3H07dJvCmzkTc4fsb4w88ddbL97Ic33sCnBQSYeBjALmGTYGwAkoSUgwDjDwjN/AGkZRSMglEwCkYBOgAAL4xMvLwqCqAAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-6075-4208","institution":"The Pennsylvania State University","correspondingAuthor":true,"prefix":"","firstName":"Huanyu","middleName":"","lastName":"Cheng","suffix":""},{"id":411353783,"identity":"e47e0f32-f883-4e55-9086-c93515f4560e","order_by":1,"name":"Ankan Dutta","email":"","orcid":"","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Ankan","middleName":"","lastName":"Dutta","suffix":""},{"id":411353784,"identity":"af77b064-2799-4bf8-b921-3f9766444e1c","order_by":2,"name":"Md Abu Sayeed Biswas","email":"","orcid":"","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Md","middleName":"Abu Sayeed","lastName":"Biswas","suffix":""},{"id":411353785,"identity":"e960050b-c6bb-4f33-8357-86e095c40138","order_by":3,"name":"Long Meng","email":"","orcid":"","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Long","middleName":"","lastName":"Meng","suffix":""},{"id":411353786,"identity":"152b7a0f-cb6f-4ba4-8d71-f7c5ee69f9aa","order_by":4,"name":"Ethan Gerhard","email":"","orcid":"","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Ethan","middleName":"","lastName":"Gerhard","suffix":""},{"id":411353787,"identity":"3658261d-4ede-4095-93f8-4e1c39f102b3","order_by":5,"name":"Arantza Moreno Calva","email":"","orcid":"https://orcid.org/0009-0002-1970-4764","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Arantza","middleName":"Moreno","lastName":"Calva","suffix":""},{"id":411353788,"identity":"0b8eb0ff-145e-401f-9744-349db1392680","order_by":6,"name":"Wanqing Zhang","email":"","orcid":"https://orcid.org/0000-0002-7298-5983","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Wanqing","middleName":"","lastName":"Zhang","suffix":""},{"id":411353789,"identity":"128d89ef-e869-43c8-bac2-30f94c7e080e","order_by":7,"name":"Abu Musa Abdullah","email":"","orcid":"","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Abu","middleName":"Musa","lastName":"Abdullah","suffix":""},{"id":411353790,"identity":"b13b1369-7ad0-4f7c-92be-9838be92ed7b","order_by":8,"name":"Lana Joharji","email":"","orcid":"","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Lana","middleName":"","lastName":"Joharji","suffix":""},{"id":411353791,"identity":"89157ad4-fffd-451a-ad0e-2a6ded119dbb","order_by":9,"name":"Yuju Che","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Yuju","middleName":"","lastName":"Che","suffix":""},{"id":411353792,"identity":"61517ed1-7f3b-4db2-ad7a-e1340d55c7ca","order_by":10,"name":"Jian Yang","email":"","orcid":"","institution":"Westlake University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Yang","suffix":""},{"id":411353793,"identity":"bd875a8b-8d2d-47f2-93d1-c1ec0558a6a8","order_by":11,"name":"Xiaogang Hu","email":"","orcid":"","institution":"The Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Xiaogang","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2025-01-14 20:45:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5829714/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5829714/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75589371,"identity":"8facfdcf-ead5-447d-afc2-b6f808e5bff3","added_by":"auto","created_at":"2025-02-06 06:54:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":647114,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic illustration of the experimental setup for neurohaptics using the ionic biogel with synergistic characteristics.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5829714/v1/4bc0adfe46d13bae1fb95d42.png"},{"id":75590034,"identity":"701267d4-b267-42b3-821e-b5fb2f913861","added_by":"auto","created_at":"2025-02-06 07:02:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":326283,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCharacterization of Ionic Biogel showing robust sol-gel transition. (a)\u003c/strong\u003e Comparison in storage and loss moduli as a function of temperature between non-ionic and ionic biogel. \u003cstrong\u003e(b)\u003c/strong\u003e Variation in the normalized viscosity from a ~1-day ionic biogel during repeated temperature cycles of ramp-up, ramp-down, and isothermal conditions. \u003cstrong\u003e(c)\u003c/strong\u003e Comparison in the thermogravimetric analysis (TGA) between the biogel and ionic biogel. \u003cstrong\u003e(d)\u003c/strong\u003e Comparison of strain-insensitivity and Young’s modulus among reported hydrogels\u003csup\u003e31–36\u003c/sup\u003e.\u0026nbsp; None of them reported self-healing properties, except for this work. \u003cstrong\u003e(e)\u003c/strong\u003e Comparison in the skin contact impedance between the ionic biogel and Ag/AgCl on beard. \u003cstrong\u003e(f)\u003c/strong\u003e CIC and permissible current amplitude across the frequency range from 0.05 Hz to 67 Hz.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5829714/v1/6a2e7ce91509f54c60f68dde.png"},{"id":75589352,"identity":"38b2b4b0-e590-46bc-b554-d62e321041dd","added_by":"auto","created_at":"2025-02-06 06:54:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":369866,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEEG characterization during mechanical and electrical stimulation. (a) \u003c/strong\u003ePower spectrogram showing increased power in the alpha regime during the eye-closing state. Schematic of the wearable electrical stimulator array placed on the arm.\u003cstrong\u003e (b) \u003c/strong\u003ePower spectrogram showing ERD during sensory mechanical vibration at Cz locations. \u003cstrong\u003e(c)\u003c/strong\u003e Variation of (force) sensation from ulnar nerve stimulation across 7 days.\u003cstrong\u003e (d) \u003c/strong\u003ePower spectrogram of EEG during electrical stimulation at 150 Hz. Power spectrum of EEG during haptic sensation applied at different frequency (5 Hz – 500 Hz) on \u003cstrong\u003e(e) \u003c/strong\u003eDay 1 and \u003cstrong\u003e(f) \u003c/strong\u003eDay 7.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5829714/v1/e5d3c5207e1e525582c38c2f.png"},{"id":75589375,"identity":"391e0cf3-82b8-4841-820a-266520902c66","added_by":"auto","created_at":"2025-02-06 06:54:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":504601,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSemi-conducting nature of Ionic Biogel. (a)\u003c/strong\u003e Schematic of tip—shaped neural interface for phase-transition, organic electrochemical transistor (OECT).\u003cstrong\u003e (b) \u003c/strong\u003eTransconductance of tip-shaped OECT at different temperatures in ionic liquid as an electrolyte, crossing the phase-transition temperature.\u003cstrong\u003e (c)\u003c/strong\u003e \u003cem\u003eI\u003c/em\u003e\u003csub\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e-V\u003c/em\u003e\u003csub\u003e\u003cem\u003eg\u003c/em\u003e\u003c/sub\u003e transfer characteristics of OECT in Phosphate Buffer Solution (PBS) solution. \u003cstrong\u003e(d)\u003c/strong\u003e Comparison in the transconductance of the temperature-dependent phase-reversible tip-shaped OECT in PBS as an electrolyte, without crossing the phase-transition OECT: 20, 25, 30, and 35°C.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5829714/v1/c8d219bd2d20c5837f7307a9.png"},{"id":94620703,"identity":"a87eb33d-39ce-410a-86b2-9ebd19e70546","added_by":"auto","created_at":"2025-10-29 04:08:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2993766,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5829714/v1/81219743-13ee-4e07-bf62-7c487492bef6.pdf"},{"id":75589356,"identity":"199dc088-f44e-4513-a9c9-c1066a2e2838","added_by":"auto","created_at":"2025-02-06 06:54:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17958691,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"SupplementaryInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-5829714/v1/786e2b7fad6aa9388a032264.docx"},{"id":75589348,"identity":"8b101b52-6134-48e1-b4ba-8acb2897ac4c","added_by":"auto","created_at":"2025-02-06 06:54:04","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":4719356,"visible":true,"origin":"","legend":"","description":"","filename":"ExtendedFigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-5829714/v1/e29aba098e72c72430ff9151.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Synergy of a Complimentary Ionic Biogel Network for Through-Hair Neurohaptics","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTransformative advancements in the field of neuroprosthetics offer hope to amputees and individuals with severe motor impairments by potentially restoring intuitive control and even sensation in prosthetic limbs\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Beyond motor control, transcutaneous electrical stimulation of peripheral nerves such as median and ulnar nerves has opened new possibilities to provide haptic feedback and enable amputees to experience projected touch sensations in their missing limbs\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. However, current evaluations of these sensations often rely on subjective self-reports, limiting the precision and repeatability that are essential to further optimize prosthetic design\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Neurohaptics provides an objective measure of neural responses to sensory stimulation to enable refined, effective haptic feedback, which can seamlessly integrate neuroprosthetics with the user's sensory perceptions\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The potential applications of neurohaptics also extend beyond prosthetics into the realm of augmented reality (AR) and virtual reality (VR), where sensory feedback could create immersive, interactive source-effector haptic experiences\u0026mdash;presenting a highly promising commercializable approach\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. This approach leverages projected sensations, enabling a seamless, comfortable AR/VR experience without compromising user immersion. Yet, as with neuroprosthetics, the field lacks consistent, objective data on neural responses to such haptic feedback, relying predominantly on subjective reports that limit the potential for standardization and optimization.\u003c/p\u003e \u003cp\u003eUnderstanding the neural mechanisms of haptic feedback during transcutaneous electrical nerve stimulation (TENS) holds promise to further advance the developments of neurohaptics. Event-related desynchronization (ERD) in the alpha or beta frequency band of electroencephalography (EEG) is a well-established biomarker of sensorimotor processing, frequently observed during tactile and mechanical stimuli such as vibration or pressure\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. However, it remains unclear whether similar ERD responses are elicited through TENS, bypassing mechanoreceptors and directly activates sensory nerves. Identifying ERD in response to TENS would indicate that the sensorimotor cortex interprets these impulses as tactile inputs, providing an objective marker for tracking neural engagement and response fidelity in haptic interfaces. Moreover, long-term TENS invokes neuroplastic mechanisms that dynamically shape sensory perception over time\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Initially, repeated stimulation can intensify perceived sensations, potentially due to synaptic strengthening and recruitment of additional neural pathways\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. However, with continued use, these sensations often diminish, reflecting neural habituation and circuit reorganization. This adaptation underscores the need for dynamic feedback systems that adjust stimulation to counteract habituation and sustain effective sensory feedback. Despite this potential, current approaches lack objective metrics for real-time monitoring of neural responses to haptic stimulation, and materials suitable for stable, long-term, and high-fidelity TENS and through-hair EEG recordings that could capture such responses.\u003c/p\u003e \u003cp\u003eTo address the persistent challenges in neurohaptics research of obtaining objective non-invasive EEG neural recording over the hair-covered motor cortex area (e.g. C3, C4, Cz) during haptic sensation, we introduce an ionic biogel network system with thermoresponsive and semiconducting characteristics, capable of concurrent high-fidelity, long-term through-hair neural recording and TENS \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea\u003cb\u003e)\u003c/b\u003e. The ionic biogel synergistically combines two material systems with independent yet complementary bonding mechanisms to result in a softer material with faster sol-gel transitions and enhanced mechanical, electrical, and electrochemical properties \u003cb\u003e(Extended\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea\u003cb\u003e)\u003c/b\u003e. In particular, the electrostatic interactions between the poly(3,4-ethylenedioxythiophene) poly(styrene sulfonate) (PEDOT:PSS) and a plasticizer such as ionic liquid, here 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM-TFSI) (ionic system)\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e are combined with the hydrogen-bonding network of the gelatin-glycerol-salt hydrogel matrix (biogel system)\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. The resulting ionic biogel addresses the challenges associated with through-hair EEG and TENS in three key aspects. First, its thermoresponsive properties (from the biogel system) provide the ionic biogel with the rapid gel-sol transition to conform to the scalp/skin upon gentle heating, thus maintaining stable, robust contact for reliable neural recording and haptic stimulation. Second, the viscoelastic flow behaviour (from the biogel system) of the ionic biogel maximizes the contact area to reduce the skin contact impedance and improve signal-to-noise ratios even upon motions due to the bioadhesive properties. Although the thermoresponsive behavior of a biogel-based system has been previously demonstrated for through-hair EEG recording, prior material systems do not possess the rapid thermoreversibility, high water retention, and electrochemical stability necessary for sustained operation over days to weeks\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Third, leveraging the semiconducting properties of PEDOT:PSS (from ionic system)\u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e, the ionic biogel can function as a thermoreversible p-type semiconductor to enable the integration of the organic electrochemical transistors (OECTs) as through-hair active electrodes with on-site amplification. Previously, OECTs have been employed for high-fidelity neural recordings\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e, but they lack thermoreversible and bioadhesive characteristics to enable a robust, through-hair EEG recording. Collectively, the unified properties of this ionic biogel enable the synthesis of bioadhesive semiconducting hydrogel-based interfaces exhibiting rapid gel-sol transitions\u0026mdash;providing stable, high-quality, long-term through-hair EEG recordings and haptic stimulation.\u003c/p\u003e \u003cp\u003eTypical polymer blending often yields a mere averaged combination of favourable properties, rather than achieving true functional synergy. In contrast, harnessing the synergy inherent in complementary material systems requires capitalizing on the spatial and compositional segregation characteristic of liquid\u0026ndash;liquid phase separation (LLPS)\u003csup\u003e\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Membraneless organelles (MLOs) in biological cells exemplify this principle: by partitioning biomolecules into distinct coexisting phases, MLOs leverage metastability and rapid, reversible transitions to integrate and optimize diverse functionalities\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Drawing inspiration from nature\u0026rsquo;s optimized LLPS-driven functionality of MLOs, the design of phase-separated ionic biogels strategically fuses dissimilar but complementary phases to realize synergy. One phase, formed from the PEDOT:PSS/EMIM-TFSI system, imparts high ionic conductivity, p-type semiconducting behavior, thermoelectricity, robust water-retention characteristics, and high electrochemical stability, enabling long-term, high-fidelity neural recording, and precise electrical stimulation. The other phase, the biopolymeric gelatin\u0026ndash;glycerol\u0026ndash;salt matrix, introduces biocompatibility, bioadhesive properties, self-healing capabilities, and thermoresponsive behaviour, and also contributes to the thermopower. Together, these coexisting phases maintain a phase-separated metastable state that allows for rapid, thermoreversible sol-gel transitions, facilitating conformality. This synergy yields an MLO-inspired, phase-separated ionic biogel with a unified combination of properties\u0026mdash;metastability, thermoreversibility, porosity, p-type semiconductivity, high air permeability, long-term stability, injectability, and strain insensitivity.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eCharacterisation of the synergistic ionic biogel network\u003c/h3\u003e\n\u003cp\u003eThe complementary properties of the ionic biogel stem from the synergistic interplay of phase-separated PEDOT:PSS/EMIM-TFSI ionic system and the gelatin-glycerol-salt hydrogel matrix \u003cb\u003e(Extended\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb\u003cb\u003e)\u003c/b\u003e. The independence of these two material systems \u003cb\u003e(Supplementary Note 1)\u003c/b\u003e minimizes unfavourable inter-network interactions, as their primary bonding mechanisms\u0026mdash;electrostatic interactions (in ionic system) and hydrogen bonds (in biogel system)\u0026mdash;operate within distinct individual phases. This arrangement exhibits metastability and phase separation, typically observed in MLOs, where compartmentalization arises from weak, dynamic interactions\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e \u003cb\u003e(Supplementary Note 2)\u003c/b\u003e. Initially, the mixture forms an amorphous state due to kinetic constraints and limited molecular mobility at room temperature; upon heating, increased chain mobility reduces the Gibbs free energy of mixing (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\varDelta\\:{G}_{mix}\\)\u003c/span\u003e\u003c/span\u003e), leading to partial miscibility\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Upon cooling, the spatial separation \u003cb\u003e(Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e)\u003c/b\u003e and difference in energy scales elevate the Gibbs free energy of mixing \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\varDelta\\:{G}_{mix}\\)\u003c/span\u003e\u003c/span\u003e, favouring phase separation and the formation of a metastable MLO-inspired composite material \u003cb\u003e(Supplementary Note 3)\u003c/b\u003e. The stable open electrochemical potential of -40 mV for \u0026gt;\u0026thinsp;7 hours \u003cb\u003e(Figure S2)\u003c/b\u003e indicates that the interface does not spontaneously homogenize because that would require overcoming significant energy barriers: interfacial tension, rearrangement of polymer chains, re-solvation or displacement of ions, and possibly changes in polymer redox states\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e \u003cb\u003e(Supplementary Note 4)\u003c/b\u003e. The molecular interactions between the gelatin-glycerol-salt hydrogel matrix and the PEDOT:PSS/EMIM-TFSI ionic system can be elucidated from a comprehensive series of characterizations \u003cb\u003e(Supplementary Note 5, Figures S3-S8, Extended\u003c/b\u003e Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea-\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eOne of the essential characteristics of the ionic biogel is a sharper gel-sol transition at ~\u0026thinsp;40\u0026deg;C to ensure rapid extrusion of the material onto the scalp. Metastability, akin to the behaviour observed in MLOs, can be experimentally validated through rapid phase transitions captured in rheological measurements\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. The storage modulus of the ionic biogel composite transitions from 7 kPa at room temperature to 3.4 kPa at scalp temperature (35\u0026deg;C) and then to a very low modulus of 60 Pa at 45\u0026deg;C \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea\u003cb\u003e)\u003c/b\u003e. This transition facilitates mechanical adaptability to flow and exert minimal strain on the scalp and surrounding hair, compared to normal biogel\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e \u003cb\u003e(Supplementary Note 6, Figures S9-S10, Extended\u003c/b\u003e Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb\u003cb\u003e)\u003c/b\u003e, following a the modified-Ellis equation for the temperature-sweep rheology \u003cb\u003e(Supplementary Note 7)\u003c/b\u003e. A cyclic thermal ramping protocol is employed to investigate the material's ability to recover its initial rheological characteristics \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb\u003cb\u003e)\u003c/b\u003e, demonstrating its metastable characteristics \u003cb\u003e(Supplementary Note 8, Figures S11-S16, Extended\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec\u003cb\u003e)\u003c/b\u003e, which can be modelled as a spring-damper model with different growth time constants to account for decay and reversibility \u003cb\u003e(Supplementary Note 9)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThe ionic biogel has distinct mechanical and adhesive properties in shear and normal direction \u003cb\u003e(Supplementary Note 10, Figures S17-S19, Extended\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed\u003cb\u003e)\u003c/b\u003e. The ionic biogel shows high water retention property (~\u0026thinsp;97% at 70\u0026deg;C) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec\u003cb\u003e)\u003c/b\u003e and water vapour transmission rate (~\u0026thinsp;1417 g/m\u003csup\u003e2\u003c/sup\u003e/day) \u003cb\u003e(Supplementary Note 11, Figure S20, Extended\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee\u003cb\u003e)\u003c/b\u003e. The synergistic interaction of thermodiffusion and thermogalvanic effects\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e in ionic biogel composite drives a high Seeback coefficient of 21 mV/K (till 3 K change) and then 4 mV/K (till 8 K change), offering promising application opportunities in low-grade thermal energy harvesting and wearable thermoelectric devices \u003cb\u003e(Supplementary Note 12, Extended\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef\u003cb\u003e)\u003c/b\u003e. The porous nature of the ionic biogel from phase separation along with the electrostatic interaction of PEDOT:PSS/ionic liquid makes it much softer than the normal biogel \u003cb\u003e(Supplementary Note 13, Figures S21, S22)\u003c/b\u003e. One of the most important benefits of phase-separation is the strain-insensitivity of the ionic biogel which only increases its resistance by 100% after reaching its strain limit of 380%, which represents the record high strain insensitivity among all types of hydrogels to our knowledge\u003csup\u003e\u003cspan additionalcitationids=\"CR32 CR33 CR34 CR35\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e \u003cb\u003e(\u003c/b\u003eFigs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed, S23\u003cb\u003e)\u003c/b\u003e. The material shows noticeable changes (\u0026gt;\u0026thinsp;1%) in resistance only after \u0026gt;\u0026thinsp;30% strain. The material also shows negligible hysteresis with resistance returning to its original value with only a 1% change.\u003c/p\u003e \u003cp\u003eThe performance of the through-hair electrophysiology hinges on the skin contact impedance through the hair \u003cb\u003e(Supplementary Note 14, Figures S24-S29, Extended\u003c/b\u003e Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea-\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed\u003cb\u003e)\u003c/b\u003e, where the impedance of 1.5 kΩ (diameter\u0026thinsp;~\u0026thinsp;2 cm) from the ionic biogel at 4 kHz is more than three orders of magnitude smaller than that of 4.4 MΩ from the commercial Ag/AgCl electrode \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee\u003cb\u003e)\u003c/b\u003e. The low skin-contact impedance shows a robust EMG signal during flexing \u003cb\u003e(Supplementary Note 15, Figures S30-S34)\u003c/b\u003e. Charge injection capacity (CIC) is one of the most crucial parameters for evaluating the performance of electrical stimulation in neuroprosthetics\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. The CIC of the ionic biogel is 10 mC/cm\u0026sup2; at 33 Hz and 5 mC/cm\u0026sup2; at 67 Hz \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef\u003cb\u003e)\u003c/b\u003e, which are comparable to existing materials used for similar applications\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e \u003cb\u003e(Supplementary Note 16, Figures S35-S40, Extended\u003c/b\u003e Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee-\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ef\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe thermoresponsive and conducting properties of the ionic biogel ensure stable, high-quality, long-term signal acquisition and reliable stimulation, even with different hair types or skin oils. An increase in EEG power amplitude during closed eyes state is observed with \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea\u003cb\u003e)\u003c/b\u003e and without sweat \u003cb\u003e(Figure S41)\u003c/b\u003e compared to open eyes state. The efficacy of the ionic biogel electrode is demonstrated through ERD in the recording of neural responses associated with motor cortex activity during mechanical or natural sensation \u003cb\u003e(Supplementary Note 17, Figures S42-S46, Extended Figs.\u0026nbsp;5a-5e)\u003c/b\u003e. The EEG power spectrum at C3 and Cz during sensory mechanical vibration (using a vortex vibrator) reveals a similar ERD trend: a reduction in beta power amplitude at Cz during weight repetitions, but no ERD reflected at C3 \u003csup\u003e9\u003c/sup\u003e \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb, \u003cb\u003eExtended Fig.\u0026nbsp;5f)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eERD has been known to occur during hand or finger movement\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, which is also consistent with mechanical vibration. However, to the best of our knowledge, no prior studies have correlated ERD with haptic sensations induced by TENS of the ulnar nerve. In this context, neural responses during cutaneous electrical stimulation are evaluated with a wearable stimulator array \u003cb\u003e(Extended Fig.\u0026nbsp;6)\u003c/b\u003e consisting of an 8\u0026times;2 grid of electrodes arranged with a constant pitch of 1.5 cm to cover the right arm \u003cb\u003e(Supplementary Note 18, Figure S47)\u003c/b\u003e. On Day 1, the perceived force sensation is increased from 0.07 N to 0.5 N as the stimulation current applied to the ulnar nerve is increased from 3.1 mA to 3.9 mA, till the subject reports perceived pain (pain threshold) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec\u003cb\u003e)\u003c/b\u003e. Notably, on Day 2, the baseline force perception at the same stimulation current of 3.1 mA increases to 0.3 N, suggesting a possible sensitization or adaptation effect within the nervous system. A decrease in the pain threshold (current amplitude at which the pain onsets) is observed on Days 4 and 7, with similar force sensations of ~\u0026thinsp;0.1 N being elicited at a significantly lower stimulation current of 2 mA. Specifically, on Day 4, a stimulation current of 3 mA can induce a sensation force that is about 842% of the value induced by the 3.1 mA stimulation on Day 1. Although the sensation force on Day 4 exhibits a similar trend and range to that observed on Day 7, there is a slight increase of ~\u0026thinsp;20% at 3 mA (the higher end of the current range). These findings indicate potential neuroplastic changes occurring over repeated stimulation sessions, possibly involving peripheral sensitization mechanisms that enhance neural responsiveness to electrical stimuli\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA significant challenge in EEG recordings during simultaneous electrical stimulation is the introduced artifacts, particularly charging artifacts resulting from current flow through the body, which can produce high-amplitude voltages (tens of millivolts range) at the scalp and contaminate the EEG signal (in microvolts range). By positioning the ground electrode along the cervical region and ulnar nerve pathway rather than behind the ear, these artifacts are reduced from approximately 40 mV to 4 mV. The artifacts are further reduced by sequential post-processing methods such as empirical mode decomposition (EMD)\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e, bandpass/notch filters, and downsampling \u003cb\u003e(Supplementary Note 19)\u003c/b\u003e. The artifact removal is generally performed using Independent Component Analysis (ICA)\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e that leverages the statistical independence of multiple channels. However, as the number of electrodes is two in this work, ICA\u0026rsquo;s performance is restricted. Therefore, EMD is utilized to decompose the signal into several intrinsic mode functions (IMFs) with the first mode corresponding to the stimulation artifacts. Similar to mechanical stimulation, ERD is also observed during electrical stimulation, which is marked by a reduction of power in alpha-wave, averaged across trials for all amplitudes \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed\u003cb\u003e)\u003c/b\u003e. Different frequency (5-500 Hz) of electrical stimulation (of amplitude of 3.7 mA) is elicited to record the change of alpha power in EEG during stimulation \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee, \u003cb\u003eSupplementary Note 20)\u003c/b\u003e. The neural response (alpha power of EEG) across different frequencies increases, reaching a maximum at 50 Hz and also around 500 Hz, corresponding to the resonant frequencies of mechanoreceptors such as Meissner Corpuscles and Pacinian corpuscles\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e respectively, as shown in other methods during mechanical/natural stimulation \u003cb\u003e(Supplementary Note 21)\u003c/b\u003e. This power attenuation \u003cb\u003e(Figure S48)\u003c/b\u003e and its spectrum across different frequencies persist on Day 7 \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDesigning through-hair active electrodes with low skin contact impedance necessitates navigating several interdependent constraints, especially when utilizing thermoresponsive, semiconducting materials that undergo gel-sol phase transitions. The multiphysics nature of the problem arises from the interplay between thermal dynamics, phase transitions, fluid mechanics, solid mechanics, and transistor physics. Notably, the viscosity of the ionic biogel depends on temperature, influencing fluid flow and ion transport within the ionic biogel domain. To simplify without the loss of generality, we focus on optimizing a tip-shaped neural interface, where the tip diameter corresponds to the channel length \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:L\\)\u003c/span\u003e\u003c/span\u003e between the source and drain of a vertical OECT \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea\u003cb\u003e)\u003c/b\u003e. In the vertical OECT localized at the tip with gold source/drain electrodes, the column is filled with a thermally conductive graphite-PDMS composite to enhance thermal transport, actively regulated by a Peltier module atop the assembly. The channel length or the diameter of the tip can be optimized as around 2.8 mm, for a 1 cm long tip which self-balances itself \u003cb\u003e(Supplementary Note 22, Figure S49)\u003c/b\u003e, also confirmed from COMSOL Multiphysics simulation \u003cb\u003e(Supplementary Note 23, Extended Figs.\u0026nbsp;7a-7c)\u003c/b\u003e. The electrical impedance and capacitance of the tip-shaped OECT are measured to be approximately 120 Ω and 40 \u0026micro;F at 100 Hz and room temperature, respectively \u003cb\u003e(Supplementary Note 24, Figure S50)\u003c/b\u003e. The decrease in the skin contact impedance improves the signal coupling \u003cb\u003e(Supplementary Note 25)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThe transconductance of the OECT exhibits a strong dependence on temperature and the choice of electrolyte. Phosphate-buffered saline (PBS), a conventional electrolyte for OECTs, tends to dehydrate at elevated temperatures, impairing ionic conductivity and device performance. To address this limitation, the ionic liquid EMIM-TFSI is employed as the electrolyte due to its high thermal stability and excellent ionic conductivity. At a drain voltage of 0.2 V, the OECT displays a maximum transconductance of 7.8 mS at 20\u0026deg;C. This transconductance increases to 35 mS at 30\u0026deg;C and further to 44 mS at 40\u0026deg;C \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb\u003cb\u003e)\u003c/b\u003e. The enhancement in transconductance with temperature can be attributed to several factors, including increased ionic mobility, thermoresponsive gelatin-glycerol matrix (decreased viscosity at higher temperatures to allow for more rapid ion diffusion and improved coupling between the gate and channel), and enhanced electronic conductivity (from increased chain mobility and enhanced π\u0026ndash;π stacking interactions). However, upon surpassing the phase transition temperature of the gelatin-glycerol matrix at approximately 42\u0026deg;C, the transconductance is dramatically decreased to 0.3 mS at 50\u0026deg;C. This sharp decline is attributed to the loss of structural integrity of the hydrogel matrix as it transitions from a gel to a sol state, causing the ionic biogel to flow. The phase transition can be avoided by operating below the phase-transition temperature, enabling phase-reversible OECTs \u003cb\u003e(Figure S51)\u003c/b\u003e. Notably, at a negative drain voltage of \u0026minus;\u0026thinsp;0.4 V, the transconductance remains low (\u0026lt;\u0026thinsp;3 mS) across the entire temperature range. This asymmetry in device behaviour suggests that the OECT is more efficient in modulating channel current through hole depletion rather than accumulation, consistent with the p-type semiconducting nature of PEDOT:PSS. A similar trend is observed when PBS is used as the electrolyte \u003cb\u003e(\u003c/b\u003eFigs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed\u003cb\u003e)\u003c/b\u003e, although the overall performance is inferior compared to EMIM-TFSI. The dehydration of PBS at higher temperatures reduces ionic conductivity and impairs the gating efficiency, leading to lower transconductance values. This comparison highlights the critical role of the ionic liquid EMIM-TFSI in maintaining high ionic conductivity and thermal stability, essential for the OECT's operation at elevated temperatures.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eLooking ahead, this work sets a foundation for further exploration into complementary material systems to develop next-generation neurointerfaces with enhanced functionality. By leveraging synergistic interactions, such as those provided by the combination of the hydrogen-bonded gelatin matrix with the PEDOT:PSS/ionic liquid domains, designs can further tune properties such as ionic conductivity, charge retention, mechanical adaptability, and durability to specific neurophysiological needs. The introduction of phase-separated, porous architectures within these materials could further augment their electrochemical performance, enabling seamless transitions between ionic and electronic conductivity within a three-dimensional, volumetric framework. Such advancements are expected to drive significant progress in the emerging field of neurohaptics, where finely-tuned materials can bridge the gap between sensory feedback and neural stimulation, offering users immersive and responsive experiences. By creating adaptive, responsive materials that closely mimic biological tissues, we are better positioned to study sensory processing, adaptation, and long-term neural plasticity. This work underscores the transformative potential of bioinspired, multifunctional materials in enabling new frontiers in neural engineering, paving the way for neuroprosthetics and wearable neurotechnologies that seamlessly integrate with human physiology.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eXPS\u003c/h2\u003e \u003cp\u003eXPS experiments were performed using a Physical Electronics VersaProbe III instrument equipped with a monochromatic Al kα x-ray source (hν\u0026thinsp;=\u0026thinsp;1,486.6 eV) and a concentric hemispherical analyzer. Charge neutralization was performed using both low-energy electrons (\u0026lt;\u0026thinsp;5 eV) and argon ions. The binding energy axis was calibrated using sputter cleaned Cu (Cu 2p3/2\u0026thinsp;=\u0026thinsp;932.62 eV, Cu 3p3/2\u0026thinsp;=\u0026thinsp;75.1 eV) and Au foils (Au 4f7/2\u0026thinsp;=\u0026thinsp;83.96 eV).\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e Peaks were charge referenced to the CHx band in the carbon 1s spectrum at 284.8 eV. Measurements were made at a takeoff angle of 45\u0026deg; with respect to the sample surface plane. This resulted in a typical sampling depth of 3\u0026ndash;6 nm (95% of the signal originated from this depth or shallower). Quantification was done using instrumental relative sensitivity factors (RSFs) that account for the x-ray cross-section and inelastic mean free path of the electrons. On homogeneous samples major elements (\u0026gt;\u0026thinsp;5 atom%) tend to have standard deviations of \u0026lt;\u0026thinsp;3% while minor elements can be significantly higher. The analysis size was ~\u0026thinsp;200 \u0026micro;m in diameter.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRaman Spectroscopy\u003c/h3\u003e\n\u003cp\u003eRaman spectroscopy was employed to investigate the surface composition and structural properties of the composite using a Horiba LabRAM HR Evolution confocal microscope equipped with a 785 nm laser and a 300 g/mm grating. The characterization was conducted across various temperatures to assess temperature-dependent changes.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFTIR\u003c/h2\u003e \u003cp\u003eFTIR measurements were conducted using a Bruker V70 spectrometer (wavenumber range: 4000 to 600 cm⁻\u0026sup1;, resolution: 6 s⁻\u0026sup1;) to examine the chemical bonding and identify organic and inorganic components in the modified nanocomposite films through infrared light. The characterization was performed at different temperatures to evaluate temperature-dependent changes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eBiocompatibility Test\u003c/h3\u003e\n\u003cp\u003eHydrogel samples were cut into circular films with 10 mm diameter and added to PBS to prepare hydrogel extracts, and 1.0 mL of the extract was put into a 24-well plate for UV irradiation. For each well containing hydrogel extract, 2\u0026times;10\u003csup\u003e4\u003c/sup\u003e MCF-10A was added and the proliferation medium was supplemented to 1.0 mL. For the wells without material, 2\u0026times;10\u003csup\u003e4\u003c/sup\u003e MCF-10A was also added and the proliferation medium was supplemented to 1.0 mL as the control group. The 24-well plate containing MCF-10A and the extract was incubated in a cell culture incubator, and 200 \u0026micro;L of proliferation medium was added to each well every two days. The proliferation of MCF-10A on the hydrogel extract on days 1 and 2 after co-culture was determined using MTT. After adding the FDA, the staining results were observed using a fluorescence microscope.\u003c/p\u003e\n\u003ch3\u003eMechanical Testing\u003c/h3\u003e\n\u003cp\u003e \u003cstrong\u003eGeneral Procedures\u003c/strong\u003e \u003cp\u003eAll mechanical and adhesive testing was conducted on an Instron J5966 testing frame (Instron, Binghamton, NY, USA) with a 1 kN load cell and utilizing Bluehill Universal mechanical testing software (Instron).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompression Testing\u003c/strong\u003e \u003cp\u003eCompression testing between parallel plates (Instron) was carried out on hydrogel specimens with a diameter of 8 mm and thickness of 1 mm to 90% strain at a strain rate of 1.3 mm/min. Initial modulus and peak stress at 90% strain were calculated from the stress profile over the initial 10% strain and the maximum stress value, respectively.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eTensile Testing\u003c/em\u003e: Tensile testing was carried out using pneumatic grips (Instron) on hydrogel samples (length \u0026times; width \u0026times; thickness: 3 cm \u0026times; 1 cm \u0026times; 1mm) at a strain rate of 50 mm/min. Initial tensile modulus, peak stress, and peak strain were calculated from the stress profile over the initial 10% of strain and the maximum stress and strain values, respectively.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eAdhesive Testing\u003c/strong\u003e \u003cp\u003eLap shear adhesive testing was carried out using pneumatic tensile grips. Strips of porcine tissue (1 cm width) were adhered in a lap configuration with an adhesive area of 1 cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and placed within the tensile grips (with the adhered region outside of the gripped area). The tensile force was then applied at a rate of 5 mm/min until adhesive failure and the maximum adhesive force was recorded. 90\u0026deg; adhesive peel testing was carried out by first gluing a porcine tissue strip (1 cm width) to a flat acrylic plate, which was then attached to the bottom compression plate of the mechanical testing frame using vice grips. Another strip of porcine tissue was adhered to this first piece using the appropriate hydrogel adhesive to create an adhesive area of 1 cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The other, free end of the second strip was then gripped by the top pneumatic grip of the testing frame, after which a tensile force was generated to the top to achieve the 90\u0026deg; peel, with adhesive force measured as above.\u003c/p\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eRheological Testing\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eGeneral Procedures\u003c/strong\u003e \u003cp\u003eAll rheological testing was conducted on a DHR-2 rheometer (TA Instruments, New Castle, DE, USA) using TRIOS software (TA Instruments) in a 20 mm parallel plate configuration (sandblasted plate faces) with a Peltier plate to control temperature. Hydrogel samples with a diameter of 20 mm and height of 1 mm were used at 25\u0026deg;C unless stated otherwise.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eShear Sweep\u003c/strong\u003e \u003cp\u003eShear sweeps were first conducted to establish the linear response region from 0.01 to 1,000% strain at a frequency of 1 Hz.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFrequency Sweep\u003c/strong\u003e \u003cp\u003eFrequency sweeps were conducted from 0.1 to 100 Hz within the linear response region (0.05% strain).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eTemperature Sweep\u003c/strong\u003e \u003cp\u003eTemperature sweeps were conducted from 25 to 60\u0026deg;C with a ramp rate of 1\u0026deg;C/min (1 Hz and 0.05% strain).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eCyclical Recovery Test\u003c/em\u003e: Cyclic recovery tests were conducted in 3 phases: an initial ramp from 25 to 60\u0026deg;C at a rate of 5\u0026deg;C/min (1 Hz and 0.05% strain), a cooling ramp from 60 to 25\u0026deg;C at a rate of 5\u0026deg;C/min (1 Hz and 0.05% strain), and a recovery interval at 25\u0026deg;C for 900 s (1 Hz and 0.05% strain). The above 3 phases were repeated over successive 4 cycles.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStimulation Procedure\u003c/h2\u003e \u003cp\u003eA 26-year-old male human subject participated in the stimulation experiment. During the experiment, the subject was comfortably seated in a chair. The electrical stimuli were delivered via a set of 2\u0026times;8 gel-based electrodes (Fig.\u0026nbsp;6 (b)). Each electrode with a diameter of 1 cm was replaced with the reported ionic biogel to enhance conductivity. The electrodes were positioned along the medial portion of the right upper arm, just beneath the short head of the biceps brachii, targeting the area near the median and ulnar nerves. This placement aligned with the way extending from the center of the armpit to the inner side of the elbow (medial epicondyle of the humerus), ensuring placement over the nerve pathways located below the skin. To deliver the electrical stimuli via a specific pair of electrodes (Fig.\u0026nbsp;6(b)), a custom-built MATLAB interface to control a switch matrix (Agilent Technologies, Santa Clara, CA) for electrode pair selection was used. The MATLAB interface can also configure the stimulation parameters of the stimulator (STG4008, Multichannel Systems, Reutlingen, Germany). Specifically, single biphasic rectangular pulses (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e(a)) were delivered to selected electrodes with a pulse width of 200 \u0026micro;s and a stimulation frequency of 150 Hz. To indicate the force evoked by stimulation, the subject's right hand was placed on a force load cell (LCM201-100N, Newark Electronics, Chicago, IL) with a sampling frequency of 1,000 Hz, allowing the subject to apply varying levels of pressure with the index finger in response to force evoked by stimulation.\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA grid search was initially performed to identify a pair of electrodes that could effectively induce flexion in at least one finger, while minimizing wrist movement and avoiding any discomfort. Once identified, this electrode pair was used for subsequent experiments. Multiple 3-s stimulation trials were conducted, with the pulse amplitude gradually increased until the subject reported discomfort. The measured forces during the plateau period were averaged to indicate the force evoked by stimulation. The evaluation of the long-term usability of the reported ionic biogel involved a series of experiments over the span of one week, specifically on Days 1, 2, 4, and 7.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eMaterials\u003c/h2\u003e \u003cp\u003eGelatin from porcine skin powder with gel strength 300 g Bloom Type A, Glycerol 99%, sodium chloride (NaCl), and the ionic liquid 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide with a concentration of 98% (HPLC) were purchased from Sigma Aldrich. PEDOT:PSS (PH 1000) in aqueous solution was purchased from Ossila.\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e For PDMS, Sylgard 184 Elastomer Base and its Curing Agent from Electron Microscopy Sciences were used at a 10:1 ratio.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePreparation of Biogel\u003c/h2\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003eOriginal Biogel\u003c/h2\u003e \u003cp\u003eThe biogel was prepared by dissolving 0.11 grams of sodium chloride in 1 mL of water. Afterward, 0.75 grams of glycerol were added and mixed, followed by adding and thorough mixing of 0.5 grams of gelatin.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e The solution was left for 2 hours so the gelatin could absorb all the components and then heated in an oven at 80\u0026ordm;C for 45 minutes. At this time, the biogel could be used as a gel with relatively liquid and highly adhesive properties. For storage or later use, the gel was left at room temperature for around 6 hours to solidify. The biogel could be heated at any time afterward to reacquire its liquid form.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eIonic Biogel\u003c/h2\u003e \u003cp\u003eThe ionic biogel was prepared by dissolving 0.11 grams of sodium chloride in 1 mL of PEDOT:PSS in an aqueous solution. Afterward, 1 mL of ionic liquid was added and mixed thoroughly.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e After 5 mins, 0.75 grams of glycerol were added and mixed, followed by adding and thorough mixing of 0.5 grams gelatin. The solution was left for 2 hours so the gelatin could absorb all the components and then heated in an oven at 80\u0026ordm;C for 45 minutes. At this time, the ionic biogel could be used as a gel in a relatively liquid form. For storage or later use, the resulting ionic biogel was left at room temperature for around 6 hours to solidify. The ionic biogel could be heated at any time afterward to reacquire its liquid and adhesive properties.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eH.C. acknowledges the support provided by NIH (Award No. R21EB030140), NSF (Grant Nos. 2319139 and 2309323), and Penn State University. A.D. acknowledges the support provided by NIH Training Grant T32NS115667, Diefenderfer Graduate Fellowship in Entrepreneurship, NSF I-Corps grant (2419142), and the Leighton Riess Graduate Fellowship at Penn State University. All human subject studies were approved by The Pennsylvania State University (protocol numbers STUDY00009245 and STUDY00021035) with the informed consent obtained from the volunteers.\u003c/p\u003e\u003ch2\u003eAuthor Contributions\u003c/h2\u003e \u003cp\u003eUnder the supervision of H.C., A.D. conceived the ideas, designed the research, synthesized the material, performed the theoretical modeling, simulations, processed the data and analysed the results. M.A.S.B. and A.M.C. optimized the material composition and prepared the electrodes, stimulating array. L.M. and X.H. developed the stimulation protocol and sensation results. A.D., E.G. and J.Y. conducted the rheological and mechanical characterization. W.Z. participated in experimental setup of thermoelectric characterization and performed UV-Vis and XPS characterization. A.M.A characterization temperature-dependent FTIR and Raman. L.J. developed electrodes. Y.C. performed biocompatibility test. A.D. and H.C. wrote the manuscript with input from all authors.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eA.D. thanks Dr. Dipankar Bhowmik from The Pennsylvania State University, University Park for the discussion on phase-separated Membraneless Organelles. We also thank Dr. Sarah Kiemle and Dr. Nichole Wonderling from Material Research Institute, The Pennsylvania State University for AFM and WAXS characterization, respectively.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAdewole DO et al (2016) The Evolution of Neuroprosthetic Interfaces. Crit Rev Biomed Eng 44:123\u0026ndash;152\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlau R et al (2024) Conductive block copolymer elastomers and psychophysical thresholding for accurate haptic effects. Sci Robot 9:eadk3925\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGupta A, Vardalakis N, Wagner FB (2023) Neuroprosthetics: from sensorimotor to cognitive disorders. Commun Biol 6:14\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlsuradi H, Park W, Eid M (2020) EEG-Based Neurohaptics Research: A Literature Review. IEEE Access 8:49313\u0026ndash;49328\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark W, Kim L, Ball T, Atashzar SF, Editorial (2022) NeuroHaptics: From Human Touch to Neuroscience. Front Neurosci 16:964014\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan Y et al (2024) On Stress: Combining Human Factors and Biosignals to Inform the Placement and Design of a Skin-like Stress Sensor. in \u003cem\u003eProceedings of the CHI Conference on Human Factors in Computing Systems\u003c/em\u003e 1\u0026ndash;13 (ACM, Honolulu HI USA, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1145/3613904.3643473\u003c/span\u003e\u003cspan address=\"10.1145/3613904.3643473\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeter J et al (2022) Movement-related beta ERD and ERS abnormalities in neuropsychiatric disorders. Front Neurosci 16:1045715\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeirovitch Y, Harris H, Dayan E, Arieli A, Flash T (2015) Alpha and Beta Band Event-Related Desynchronization Reflects Kinematic Regularities. J Neurosci 35:1627\u0026ndash;1637\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYakovlev L, Syrov N, Miroshnikov A, Lebedev M, Kaplan A (2023) Event-Related Desynchronization Induced by Tactile Imagery: an EEG Study. \u003cem\u003eeneuro\u003c/em\u003e 10, ENEURO.0455-22.2023\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeijora AC, Back AP, Fr\u0026eacute;z AR, Azevedo MRB, Bertolini G (2023) R. F. Peripheral electrical stimulation on neuroplasticity and motor function in stroke patients: a systematic review and meta-analysis. Neurol Res 45:1111\u0026ndash;1126\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeesen RLJ, Cuypers K, Rothwell JC, Swinnen SP, Levin O (2011) The effect of long-term TENS on persistent neuroplastic changes in the human cerebral cortex. Hum Brain Mapp 32:872\u0026ndash;882\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCuypers K, Levin O, Thijs H, Swinnen SP, Meesen RL (2010) J. Long-Term TENS Treatment Improves Tactile Sensitivity in MS Patients. Neurorehabil Neural Repair 24:420\u0026ndash;427\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y et al (2017) A highly stretchable, transparent, and conductive polymer. Sci Adv 3:e1602076\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang C et al (2022) On-skin paintable biogel for long-term high-fidelity electroencephalogram recording. Sci Adv 8:eabo1396\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLan L et al (2024) Skin-Inspired All‐Natural Biogel for Bioadhesive Interface. Adv Mater 36:2401151\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRivnay J et al (2015) High-performance transistors for bioelectronics through tuning of channel thickness. Sci Adv 1:e1400251\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhodagholy D et al (2013) High transconductance organic electrochemical transistors. Nat Commun 4:2133\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRivnay J et al (2018) Organic electrochemical transistors. Nat Rev Mater 3:17086\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRivnay J et al (2016) Structural control of mixed ionic and electronic transport in conducting polymers. Nat Commun 7:11287\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpyropoulos GD, Gelinas JN, Khodagholy D (2019) Internal ion-gated organic electrochemical transistor: A building block for integrated bioelectronics. Sci Adv 5:eaau7378\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCea C et al (2020) Enhancement-mode ion-based transistor as a comprehensive interface and real-time processing unit for in vivo electrophysiology. Nat Mater 19:679\u0026ndash;686\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuan C, Wang RA (2024) Unified Description of Salt Effects on the Liquid\u0026ndash;Liquid Phase Separation of Proteins. ACS Cent Sci 10:460\u0026ndash;468\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrangwynne CP et al (2009) Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation. Science 324:1729\u0026ndash;1732\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J et al (2024) Metastable biological matter in liquid phase separation. Appl Res 3:e202300071\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi L, Hou Z (2022) Theoretical modelling of liquid\u0026ndash;liquid phase separation: from particle-based to field-based simulation. Biophys Rep 8:55\u0026ndash;67\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirose T, Ninomiya K, Nakagawa S, Yamazaki T (2023) A guide to membraneless organelles and their various roles in gene regulation. Nat Rev Mol Cell Biol 24:288\u0026ndash;304\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y et al (2024) Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications. Signal Transduct Target Ther 9:305\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFritsch AW et al (2021) Local thermodynamics govern formation and dissolution of \u003cem\u003eCaenorhabditis\u003c/em\u003e elegans P granule condensates. \u003cem\u003eProc. Natl. Acad. Sci.\u003c/em\u003e 118, e2102772118\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi X (2022) Constrictions Induced Metastability and Kinetic Stability for Advanced Solid-State Battery Design. in \u003cem\u003eEncyclopedia of Energy Storage\u003c/em\u003e 180\u0026ndash;190Elsevier. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/B978-0-12-819723-3.00052-4\u003c/span\u003e\u003cspan address=\"10.1016/B978-0-12-819723-3.00052-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan C-G et al (2020) Giant thermopower of ionic gelatin near room temperature. Science 368:1091\u0026ndash;1098\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou T et al (2023) 3D printable high-performance conducting polymer hydrogel for all-hydrogel bioelectronic interfaces. Nat Mater 22:895\u0026ndash;902\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y et al (2020) Morphing electronics enable neuromodulation in growing tissue. Nat Biotechnol 38:1031\u0026ndash;1036\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu S et al (2024) Spider-silk-inspired strong and tough hydrogel fibers with anti-freezing and water retention properties. Nat Commun 15:4441\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao W et al (2023) Road Narrow-Inspired Strain Concentration to Wide‐Range‐Tunable Gauge Factor of Ionic Hydrogel Strain Sensor. Adv Sci 10:2303338\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei H et al (2021) Orthogonal photochemistry-assisted printing of 3D tough and stretchable conductive hydrogels. Nat Commun 12:2082\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao Y et al (2020) Hierarchically Structured Stretchable Conductive Hydrogels for High-Performance Wearable Strain Sensors and Supercapacitors. Matter 3:1196\u0026ndash;1210\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGanji M, Tanaka A, Gilja V, Halgren E, Dayeh SA (2017) Scaling Effects on the Electrochemical Stimulation Performance of Au, Pt, and PEDOT:PSS Electrocorticography Arrays. Adv Funct Mater 27:1703019\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeng J et al (2024) A bioadhesive pacing lead for atraumatic cardiac monitoring and stimulation in rodent and porcine models. Sci Transl Med 16:eado9003\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhuang N et al (2017) Emotion Recognition from EEG Signals Using Multidimensional Information in EMD Domain. \u003cem\u003eBioMed Res. Int.\u003c/em\u003e 8317357 (2017)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHyv\u0026auml;rinen A (2013) Independent component analysis: recent advances. Philos Trans R Soc Math Phys Eng Sci 371:20110534\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLipomi DJ, Dhong C, Carpenter CW, Root NB, Ramachandran VS (2020) Organic Haptics: Intersection of Materials Chemistry and Tactile Perception. Adv Funct Mater 30:1906850\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlavin MT et al (2024) Bioelastic state recovery for haptic sensory substitution. Nature 635:345\u0026ndash;352\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeah MP (2001) Summary of ISO/TC 201 Standard: VII ISO 15472: 2001\u0026mdash;surface chemical analysis\u0026mdash;x-ray photoelectron spectrometers\u0026mdash;calibration of energy scales. Surf Interface Anal 31:721\u0026ndash;723\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShin H, Watkins Z, Huang H, Helen), Zhu Y, Hu X (2018) Evoked haptic sensations in the hand via non-invasive proximal nerve stimulation. J Neural Eng 15:046005\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5829714/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5829714/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eUnderstanding the neural mechanisms underlying haptic sensations is crucial for advancing neuroprosthetics. However, achieving on-site amplification non-invasively through-hair neural recordings remains a significant challenge as it requires thermoreversible, bioadhesive, and semiconducting characteristics in the same material. Typical polymer composite compromises on complementary properties. To address this, we present a membraneless organelles - inspired ionic biogel that leverages liquid\u0026ndash;liquid phase separation. This enables a unique synergy of complementary properties, including rapid thermoreversible transitions, p-type semiconductivity, thermoelectricity, enhanced electrochemical stability, self-healing, and bioadhesive capabilities. These characteristics enable to analyze the frequency dependence of event-related desynchronization during electrical stimulation over days mimicking the frequency response of mechanoreceptors sensation. This thermoresponsive, semiconducting ionic biogel also enables a phase-reversible, self-balancing, tip-shaped vertical organic electrochemical transistor with a high transconductance of 44 mS at 40\u0026deg;C. The ionic biogel demonstrates synergistic complementary properties to understand through-hair neurohaptics.\u003c/p\u003e","manuscriptTitle":"Synergy of a Complimentary Ionic Biogel Network for Through-Hair Neurohaptics","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-06 06:53:32","doi":"10.21203/rs.3.rs-5829714/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"845bbe5d-034c-4055-aca6-707ab9dfbc44","owner":[],"postedDate":"February 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":43859869,"name":"Physical sciences/Materials science/Soft materials/Gels and hydrogels"},{"id":43859870,"name":"Physical sciences/Engineering/Biomedical engineering"},{"id":43859871,"name":"Physical sciences/Materials science/Materials for devices/Sensors and biosensors"}],"tags":[],"updatedAt":"2025-10-29T02:41:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-06 06:53:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5829714","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5829714","identity":"rs-5829714","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}