Biology subjects

Illa, X.

Publications and source records attributed to Illa, X..

8 recordsLinked to original sources

bioRxiv2026

Advances in Thin-Film Graphene Neurotechnology for Chronic Nerve Stimulation and Recording

Neurotechnology is being explored for restoring sensorimotor functions after paralysis or amputation, which requires peripheral nerve interfaces that are selective, bidirectional, and chronically stable. Reduced graphene oxide (rGO)-based microelectrodes offer low impedance and a high charge-injection limit; however, long-term in vivo performance has been limited by the durability of encapsulation. Here, we introduce a 10 {micro}m-thick transverse intrafascicular multichannel electrode (TIME) with a hybrid polyimide-Al2O3 encapsulation engineered to improve fabrication yield, electrode-to-electrode uniformity, and device stability. In vitro, devices maintained near-ideal capacitive behaviour after accelerated ageing (3 months in PBS at 57 {degrees}C) and sustained 109 biphasic stimulation pulses without detectable electrochemical degradation. In vivo, the arrays recorded compound nerve action potentials after one month and enabled selective activation of distinct peripheral nerve fibres with comparatively low current thresholds during four months of follow-up, remaining below the device maximum injectable current. Together, these results demonstrate that combining graphene microelectrodes with a thin hybrid encapsulation improves chronic reliability of intraneural thin-film interfaces and helps to close the gap between laboratory prototypes and clinically relevant neuroprosthetic systems.

bioengineering↗

bioRxiv2025

Low-temperature integration of printed electrochemical sensors into OSTE+ micrfluidics for oxygen monitoring and sensing

Real-time monitoring of biological events is essential for advancing in drug testing, disease modeling, and precision medicine. However, conventional analytical methods often lack the spatiotemporal resolution to capture dynamic cellular responses, particularly in Organ-on-a-Chip (OoC) platforms and microphysiological systems (MPS). While progress has been made in sensor development, integrating sensors into microfluidic devices remains technically challenging. Materials commonly used in microfluidics, such as polydimethylsiloxane (PDMS), are poorly suited for stable sensor integration due to low metal adhesion. Off-stoichiometry thiol-ene-epoxy (OSTE+) polymers present a promising alternative due to the presence of unreacted thiol groups. These groups enable dual functionalities: strong metal affinity for direct for robust sensor integration, and oxygen scavenging essential for microscale oxygen level control. However, their compatibility with conventional sensor fabrication methods, particularly those requiring elevated temperatures, is limited. This work introduces a low-temperature fabrication method based on inkjet printing and photonic curing, suitable for thermally sensitive substrates. Gold and silver nanoparticle inks were directly sintered onto OSTE+ using photonic curing, producing functional electrochemical sensors for spatially resolved and real-time oxygen detection. Unlike conventional thermal sintering, which is incompatible with many microfluidic materials, photonic curing preserves the chemical reactivity and mechanical properties of the polymer without requiring surface treatment or adhesive layers. To demonstrate functionality, sensors were integrated into microfluidic devices for continuous monitoring of dissolved oxygen. Real-time oxygen depletion driven by the materials intrinsic scavenging capability was successfully quantified. These findings support the compatibility of sensor integration into OSTE+ polymers enhancing the real-time monitoring capabilities in OoC and MPS systems. HighlightsO_LIInkjet-printed sensors are integrated into OSTE+ using a low-temperature protocol. C_LIO_LIPhotonic curing enables sintering of gold and silver nanoparticle inks without damaging the polymer substrate. C_LIO_LIOxygen scavenging is monitored in real time using integrated electrochemical sensors. C_LIO_LITunable oxygen gradients are achieved in OSTE+ microfluidics for organ-on-chip models. C_LI

bioengineering↗

bioRxiv2025

Graphene Micro-transistor Arrays Reveal Perfusion-Dependent Electrophysiological and Haemodynamic Signatures of Cortical Spreading Depolarizations in Ischaemic Stroke

Cortical spreading depolarizations (CSDs) are large-scale disruptions of neuronal homeostasis that contribute to secondary injury in ischaemic stroke. In healthy cortex, CSDs induce vasodilation to meet metabolic demand, whereas in ischaemic tissue, they can provoke vasoconstriction and sustained hypoperfusion, exacerbating damage. We present a multimodal neurotechnology platform integrating flexible, transparent graphene solution-gated field-effect transistor (gSGFET) arrays with laser speckle contrast imaging (LSCI), enabling simultaneous DC-coupled electrophysiological recordings and cerebral blood flow imaging with high spatiotemporal fidelity. gSGFETs enable stable, distortion-free recording of infraslow potentials essential for resolving CSD waveforms in vivo. In two murine stroke models, we show that CSD waveform duration and morphology scale with local perfusion, delineating electrophysiological subtypes predictive of tissue viability and haemodynamic response. In metabolically compromised cortex, CSDs exhibit double peaks or negative ultraslow components that result in vasoconstriction, contrasting with narrow, monophasic waveforms eliciting vasodilation in healthy regions. Systemic ketamine shortens CSD duration and converts vasoconstriction to vasodilation in perfusion-deficit tissue, revealing a mechanism for its neuroprotective action. This platform enables high-fidelity investigation of brain-blood flow interactions in vivo.

neuroscience↗

bioRxiv2024

Large-scale infra-slow dynamics of extracellular potentials linked to synchronous states revealed by graphene neural probes

Infra-slow (<0.5 Hz) brain dynamics reflect homeostatic and neuromodulatory processes that modulate neuronal excitability and shape faster oscillations across brain regions. Infra-slow brain activity is typically inferred from magnetic or optical imaging, but these methods are limited in temporal resolution and compatibility with unconstrained behavior. Infra-slow local field potentials (isLFPs) could provide a direct measure of infra-slow network dynamics, but have remained poorly characterized due to the absence of scalable, DC-coupled recording methods. Here, we introduce DC-coupled electrophysiological imaging based on arrays of up to 512 multiplexed graphene transistors enabling stable, high-density recordings across cortical regions and cortical layers in freely moving rats. We developed an analytical framework for the analysis of wide-band LFP, revealing that synchronous oscillatory states of variable duration and spatial scale are consistently linked to topographically and translaminarly structured DC potential shifts. We propose a physiological model linking these DC shifts to sustained gradients of extracellular K+ concentration, providing a mechanistic connection between neuronal synchrony and isLFP dynamics. By integrating DC-coupled sensing, multiplexed scalability, and depth-surface co-registration, this work establishes a new modality for imaging-like electrophysiology in freely moving animals and a framework for interpreting infra-slow dynamics.

neuroscience↗

bioRxiv2024

Flexible graphene-based neurotechnology for high-precision deep brain mapping and neuromodulation in Parkinsonian rats

Deep brain stimulation (DBS) is a neuroelectronic therapy for the treatment of a broad range of neurological disorders, including Parkinsons disease. Current DBS technologies face important limitations that impact their efficacy, such as large electrode size, invasiveness, and lack of adaptive therapy based on biomarker monitoring. The use of novel electrode materials is expected to contribute to overcome these limitations. In a previous study, we reported that nanoporous reduced graphene oxide (rGO) is a promising electrode material due to its high charge injection capacity and low impedance. Here, we investigate the potential benefits of using the rGO technology in DBS. To this end, we implant a flexible high-density array of rGO microelectrodes in the subthalamic nucleus (STN) of healthy and hemi-parkinsonian rats to investigate specific electrophysiological Parkinsonian biomarkers and to assess the effect of microscale stimulation. We demonstrate that these microelectrodes record action potentials with high signal-to-noise ratios (SNR > 6), allowing the precise localization of deep brain structures like the STN, and the tracking of multiunit-based biomarkers such as STN bursts. The bidirectional capability to deliver high-density focal stimulation and to record high-fidelity signals unlocks the visualization of the local neuromodulation of the multiunit biomarker. These findings demonstrate the potential of bidirectional high-resolution neural interfaces to investigate the mechanisms around DBS in preclinical models and suggest new avenues for the use of adaptive closed-loop operation based on electrophysiological biomarkers monitoring.

bioengineering↗

bioRxiv2022

Graphene-based thin film microelectrode technology for in vivo high resolution neural recording and stimulation

Neuroprosthetic technology aims to restore nervous system functionality in cases of severe damage or degeneration by recording and stimulating the electrical activity of the neural tissue. One of the key factors determining the quality of the neuroprostheses is the electrode material used to establish electrical communication with the neural tissue, which is subject to strict electrical, electrochemical, and mechanical specifications as well as biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin film technology and its engineering to form flexible neural implants. Bench measurements show that the developed microelectrodes offer low impedance and high charge injection capacity throughout millions of pulses. In vivo electrode performance was assessed in rodents both from brain surface and intracortically showing high-fidelity recording performance, while stimulation performance was assessed with an intrafascicular implant that demonstrated low current thresholds and high selectivity for activating subsets of axons within the sciatic nerve. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical and intraneural implantation. Overall, this works describes a novel graphene-based thin film microelectrode technology and demonstrates its potential for high-precision neural interfacing in both recording and stimulation applications.

bioengineering↗

bioRxiv2022

Epithelial monolayer development and tight junction assembly on nanopillar arrays

Nanostructured materials provide an outstanding opportunity to both stimulate and measure cellular processes. In the context of tight junctions, it was previously reported that transient application of a nanotopographic surface over the apical brush border membrane of epithelial monolayers triggers redistribution of ZO-1, claudins, and F-actin that increases paracellular macromolecular flux. In excitable tissues, nanomaterials have been used to apply and measure electrical signals, such action potentials. As a first step towards translating these technologies for use in analysis of epithelial function, we sought to culture monolayers composed of transporting epithelia over nanopillar arrays without perturbing cellular structure or function. Madin-Darby Canine kidney I (MDCK I) cells were cultured on collagen-coated silicon chips with [~]1 m diameter nanopillar arrays. Fluorescence and scanning electron microscopy were used to assess the impact of height on nanopillar-epithelial interactions. Monolayers formed over and were largely unaffected by short nanopillars. These nanopillars were located beneath basal epithelial surfaces and were not preferentially located within lateral intercellular spaces or beneath ZO-1-containing junctions. In contrast, tall nanopillars that exceeded cell height disrupted MDCK I monolayer growth. Cells interacted with, encircled, and extended cytoplasm over the top of tall nanopillars, and dense ZO-1 and F-actin accumulations occasionally surrounded apical membranes adjacent to nanopillars. Finally, when grown over arrays composed of nanopillars 1 - 2 m shorter than cells, MDCK I frequently grew between nanopillars. As a result, nanopillars were more commonly present within lateral intercellular spaces beneath junctions. Apical complex structure was intact, as assessed by fluorescence microscopy of ZO-1, occludin, claudin-2, F-actin, and E-cadherin. Apical microvilli were also unaffected. We therefore show that conditions can be defined to allow growth of mature, correctly assembled epithelial monolayers with nanopillars localized to lateral intercellular spaces. This sets the stage for application of nanotechnologies for perturbation and analysis of epithelial biology.

cell biology↗

bioRxiv2021

Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes

Mapping the entire frequency bandwidth of neuronal oscillations in the brain is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously infraslow activity (<0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. However, commonly used metal microelectrode technology is not well suited for recording infraslow activity. Here we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record infraslow and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, post-ictal spreading depolarisation, and high frequency epileptic activity through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. We demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow activity in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, in particular, to examine the contributions of infraslow activity to seizure initiation and termination.

neuroscience↗