Biology subjects

Malliaras, G. G.

Publications and source records attributed to Malliaras, G. G..

14 recordsLinked to original sources

bioRxiv2026

SpiraMed: A Stereotactic Helix-based Therapy Delivery system for the Human Brain

Stereotactic needle-based delivery remains the standard for local administration of Advanced Therapy Medicinal Products (ATMPs) to the human brain. ATMP administration typically involves multiple trajectories, presenting cumulative risks and prolonging surgery. Reflux-prone, patchy therapy coverage compromises clinical results. We demonstrate a novel approach, deploying a helical delivery catheter via a single access trajectory per target, referred to as SpiraMed. Helix retraction is synchronised with therapy delivery, enabling comprehensive target coverage in seconds. Helix pitch and diameter can be precisely tailored to patient-specific target volume and vascular anatomy, as part of the preoperative stereotactic surgical planning process. Testing in agarose phantoms, live sheep and cadaveric human brain confirms enhanced therapy delivery volume, delivery speed and target coverage, with reductions in reflux and predicted risk of bleeding complication. SpiraMed represents a new paradigm, promising to help deliver on the transformative potential of cell and gene therapies across the spectrum of human CNS disease.

bioengineering↗

bioRxiv2026

A Dual-Gate OECT Platform for Drift-Suppressed and High-Sensitivity Real-Time Biosensing

Organic electrochemical transistors (OECTs) enable high transconductance at low operating voltages through the volumetric charging of organic mixed ionic/electronic conductors (OMIECs), making them attractive transducers for biosensing. However, the same ionic -electronic coupling makes OMIECs, such as poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS), sensitive to different ions and various environmental fluctuations, so drift and memory effects may compromise the quantitative readout in complex biofluids. In this work, we introduce a novel OECT-based sensor configuration that minimises drift by addressing a single channel with two gates: a functionalised sensing gate and a reference gate that allows real-time decoupling of environmental and channel-state fluctuations. A pulsed gate-biasing protocol is introduced to promote channel conductivity recovery and mitigate state accumulation. Using enzymatic glucose sensing as a proof of concept, the platform suppresses time-dependent drift by ~96%, eliminates temperature-induced variations up to 99% across the 20-70 {degrees}C range, improves calibrated sensitivity by 55% and reduces interferent-induced deviations under physiologically relevant conditions. By improving both signal stability and analytical reliability, this strategy addresses a central limitation of OECT biosensors and advances their use in high-sensitivity point-of-care biosensing in complex biological environments.

bioengineering↗

bioRxiv2026

Integrating Electrical Components into a Printed Self-folding Cuff Electrode for Chronic Peripheral Nerve Interfaces

Neuroelectronic thin-film implants hold promise for advancing fundamental understanding of the peripheral nervous system and offer potential for targeted treatments using specific stimulation. However, challenges in establishing robust and durable connections to soft and flexible implants limit their widespread adoption and long-term utility. Here, we present a novel method for integrating rigid electrical components, such as a standard USB-C connector, directly into a printed stretchable self-folding cuff electrode for chronic peripheral nerve interfacing. Our multi-material printing approach provides a gradual stiffness transition, effectively mitigating common failure points associated with mechanical stress at soft-rigid boundary. We demonstrate the integration of a wireless stimulation circuit and a robust USB-C implantable port, offering a plug- and-play solution for stable chronic electrophysiology experiments. Chronic implant studies in free-running locusts with USB-C connectors show reliable nerve recordings, capturing behavioral differences. The concept is further validated as a transcutaneous implanted port in rats for vagus nerve recordings. This work addresses a critical bottleneck in neurotechnology by enabling robust connectivity for implanted devices, which is essential for advancing peripheral nervous electrophysiology experiments in freely moving small vertebrates and insects.

neuroscience↗

bioRxiv2025

PEDOT:PSS conducting eutectogel for enhanced electrical recording and stimulation in implantable neural interfaces

Conductive polymers such as PEDOT:PSS are widely used in bioelectronic interfaces due to their mixed ionic-electronic conductivity and biocompatibility. However, their mechanical fragility and limited processability constrain their performance in implantable devices. Deep eutectic solvents (DES), when combined with PEDOT:PSS, form eutectogels that enable thick, soft coatings. Here, we present a PEDOT:PSS-based eutectogel incorporating choline chloride: lactic acid and GOPS, integrated into flexible thin-film electrode arrays for sciatic nerve interfacing. These implants feature an array of electrodes and a pre-formed spiral geometry to conformally wrap small-diameter nerves. Devices were fabricated using standard photolithography and reactive ion etching techniques, allowing side-by-side comparison of PEDOT:PSS/DES with conventional PEDOT:PSS electrodes. PEDOT:PSS/DES enabled single-layer films up to 800 nm thick, significantly greater than PEDOT:PSS, and yielding over two-fold improvements in impedance and charge injection capacity in vitro. Acute in vivo electrophysiology in rats confirmed enhanced neural recording and stimulation capabilities, with lower impedance, higher capacitance, and reduced motor activation thresholds. While PEDOT:PSS/DES more reliably elicited motor responses at lower stimulation currents, electromyogram signal amplitudes from the tibialis anterioris at matched stimulation levels were comparable between materials. These results suggest that while superior electrochemical properties improve neural interface performance, local electrode-tissue interactions remain critical. Overall, this work establishes DES-modified PEDOT:PSS as a promising electrode material for soft neural interfaces and highlights its potential for advancing implantable bioelectronics.

neuroscience↗

bioRxiv2025

NeuroSuite for Long-term Functional and Structural Studies of Air-Liquid Interface Cerebral Organoids

Over the past decade, air-liquid interface cerebral organoids (ALI-COs) have emerged as powerful in vitro models that capture essential structural and functional traits of the human brain, offering an exciting alternative to traditional animal models in neuroscience. Yet, the full potential of these systems has remained untapped due to the lack of non-invasive, long-term electrophysiological tools capable of preserving organoid integrity. Existing techniques, ranging from patch clamping to rigid and 3D microelectrode arrays, often compromise organoid growth and disrupt delicate cytoarchitecture. Here, we present NeuroSuite, an innovative bioelectronic platform designed to overcome these challenges. At its core is Neuroweb, a perforated, ultra-thin, and conformable organic microelectrode array engineered for minimal disruption of nutrient and oxygen exchange. Neuroweb is reusable and supports stable recordings for over six months, making it uniquely suited for longitudinal studies. Coated with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a high-performance mixed ionic-electronic conductor, Neuroweb delivers exceptional signal-to-noise ratio recordings with high spatial precision. By pairing Neuroweb with NeuroMaps, an intuitive software for interactive analysis and visualisation, NeuroSuite enables long-term, non-invasive tracking and spatial mapping of electrical activity from brain organoids and ex vivo brain slices at the air-liquid interface. Following rigorous validation, we demonstrate that NeuroSuite can capture both high- and low-frequency throughout maturation. Our pipeline reveals evolving network connectivity, including the development of GABA-ergic interneurons, and concurrent shifts in high-frequency spiking and low-frequency oscillations indicative of a refinement in the excitatory-inhibitory balance. Finally, automated data acquisition and spatial spike mapping highlight local activity changes in response to media composition, a factor often overlooked in conventional recordings. NeuroSuite thus opens a new frontier in organoid neuroscience, enabling precise, long-term monitoring essential for modelling neurological diseases, understanding human brain development, and accelerating drug discovery. TeaserConformal organic bioelectronic arrays, combined with an open-access toolbox for analysis and visualisation, reveal real-time and long-term neural dynamics in brain organoid slices at the air-liquid interface.

neuroscience↗

bioRxiv2024

Development of novel signal and spike velocity analysis tools in peripheral nerve cuffs

ObjectivePeripheral nerve neurotechnologies hold significant promise as avenues for new closed-loop clinical treatments. However, analysis tools for nerve recordings - a key component of closed-loop nerve technologies - remain underdeveloped compared to brain-focused methods. This study introduces and explores the performance of two novel nerve signal analysis techniques which rely on a defining feature of peripheral nerve signals: the reliable conduction velocity of signals transmitted by axons in nerves. ApproachWe test the capabilities of the introduced cross-correlation and spike delay velocity analysis techniques both in silico on synthetic nerve signals and on in vivo nerve signals acquired from freely-moving rats. Main resultsOur findings show that both techniques can be successfully employed to extract transmission direction and velocity information from nerve cuff recordings. Notably, cross-correlation analysis can be employed to detect neural signals of very low signal-to-noise ratio, otherwise undetectable by typical spike detection approaches. SignificanceOur findings provide new techniques to both enhance detection and extract new information in the form of velocity data from nerve recordings. As axon signal conduction direction and velocity is tightly linked to neural function, these techniques can support new research into peripheral nervous system function and new therapeutic approaches driven by neural interfaces.

neuroscience↗

bioRxiv2024

Implantable Bioelectronics for Real-time in vivo Recordings of Enteric Neural Activity

The gastrointestinal tract is regulated by a complex network of electrically-active cell types that communicate to drive gut function. One of these systems, the enteric nervous system, represents a primary point of contact for a host of factors that influence bodily health and behavior. This division of the autonomic nervous system is unique in both its extensivity, with neurons distributed throughout the gastrointestinal tract from the esophagus to the rectum, and its capability for local information processing. However, the constant intrinsic and extrinsic motion of the gut as well as the sparse distribution of the neurons that constitute the enteric nervous system has made, access and analysis for study of this important component of the gastrointestinal tract exceedingly challenging. Here, we present the construction and validation of a bioelectronic implant for accessing neural information from the distal colon. The implant, constructed for compatibility with a novel surgical approach applicable across multiple species, is designed to be positioned within the colonic wall in close proximity to the enteric nervous plexi. We captured complex multi-frequency electrophysiological responses to neural chemical stimulants and showed that we can record distension activity mimicking gut motility. We also show the feasibility of utilizing this device for recording from putative single neurons in freely-moving rats and examining colonic activity in the context of food intake and stress. This work marks a significant advancement in understanding the complex pathways of the gut-brain axis. Our bioelectronic monitoring system demonstrates the power of real-time electrophysiological monitoring for the distal areas of the autonomic nervous system. Furthermore, direct access to the communication pathways of the enteric nervous system paves the way for novel neuromodulation strategies targeting the gut-brain axis.

neuroscience↗

bioRxiv2024

Machine learning-based spike sorting reveals how subneuronal concentrations of monomeric Tau cause a loss in excitatory postsynaptic currents in hippocampal neurons

Extracellular recordings of neuronal activity constitute a powerful tool for investigating the intricate dynamics of neural networks and the activity of individual neurons. Microelectrode arrays (MEAs) allow for recordings with a high electrode count, ranging from 10s to 1000s, generating extensive datasets of neuronal information. Furthermore, MEAs capture extracellular field potentials from cultured cells, resulting in highly complex neuronal signals that necessitate precise spike sorting for meaningful data extraction. Nevertheless, conventional spike sorting methods face limitations in recognising diverse spike shapes, thereby constraining the full utilisation of the rich dataset acquired from MEA recordings. To overcome these limitations, we have developed a machine learning algorithm, named PseudoSort, which employs advanced self-supervised learning techniques, a distinctive density-based pseudo-labelling strategy, and an iterative fine-tuning process to enhance spike sorting accuracy. Through extensive benchmarking on large-scale simulated datasets, we demonstrate the superior performance of PseudoSort compared to recently developed machine learning-based (ML) spike sorting algorithms. We showcase the practical application of PseudoSort by utilising MEA recordings from hippocampal neurons exposed to subneuronal concentrations of monomeric Tau, a protein associated with Alzheimers disease (AD). Our results, validated against patch clamp experiments, unveil that monomeric Tau at subneuronal concentrations induces stimulation-dependent disruptions in both local and global activity of hippocampal neurons. Remarkably, patch clamp electrophysiology highlights the effect of combined Tau and neuronal stimulation treatment on excitatory postsynaptic currents, whereas PseudoSort excels in identifying neuronal clusters that exhibit diminished firing capacity following Tau treatment alone, i.e., in the absence of stimulation. This comprehensive approach validates the prowess of PseudoSort and unravels the intricate effects of Tau on neuronal activity, particularly in the context of AD.

neuroscience↗

bioRxiv2023

Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions

Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with an ultraconformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices recorded nerve action potentials with fascicle-specific resolution and extracted from these the conduction velocity and direction of propagation. The ultraconformable cuffs exhibited high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices were able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.

neuroscience↗

bioRxiv2022

3D Bioelectronics with a Remodellable Matrix for Long-term Tissue Integration and Recording

Bioelectronics hold the key for understanding and treating disease. However, achieving stable, long-term interfaces between electronics and the body remains a challenge. Implantation of a bioelectronic device typically initiates a foreign body response, which can limit long-term recording and stimulation efficacy. Techniques from regenerative medicine have shown a high propensity for promoting integration of implants with surrounding tissue, but these implants lack the capabilities for the sophisticated recording and actuation afforded by electronics. Combining these two fields can achieve the best of both worlds. Here, we show the construction of a hybrid implant system for creating long-term interfaces with tissue. We create implants by combining a microelectrode array with a bioresorbable and remodellable gel. These implants are shown to produce a minimal foreign body response when placed into musculature, allowing us to record long-term electromyographic signals with high spatial resolution. This device platform drives the possibility for a new generation of implantable electronics for long-term interfacing.

bioengineering↗

bioRxiv2022

Pulsed transistor operation enables miniaturization of electrochemical aptamer based sensors

By simultaneously transducing and amplifying, transistors offer advantages over simpler, electrode-based transducers in electrochemical biosensors. However, transistor-based biosensors typically use static (i.e., DC) operation modes that are poorly suited for sensor architectures relying on the modulation of charge transfer kinetics to signal analyte binding. Thus motivated, here we translate the AC "pulsed potential" approach typically used with electrochemical aptamer-based sensor to an organic electrochemical transistor (OECT). Specifically, by applying a linearly sweeping square-wave potential to an aptamer-functionalized gate electrode, we produce current modulation across the transistor channel two orders of magnitude larger than seen for the equivalent, electrode-based biosensor. Critically, the resulting amplification is scalable, such that there is no signal loss with OECT miniaturization. The pulsed transistor operation demonstrated here could be applied generally to sensors relying on kinetics-based signaling, expanding opportunities for non-invasive and high spatial resolution biosensing.

bioengineering↗

bioRxiv2020

A mouse bio-electronic nose for sensitive and versatile chemical detection

When it comes to simultaneous versatility, speed, and specificity in detecting volatile chemicals, biological olfactory systems far outperform all artificial chemical detection devices. Consequently, the use of trained animals for chemical detection in security, defense, healthcare, agriculture, and other applications has grown astronomically. However, the use of animals in this capacity requires extensive training and behavior-based communication. Here we propose an alternative strategy, a bio-electronic nose, that capitalizes on the superior capability of the mammalian olfactory system, but bypasses behavioral output by reading olfactory information directly from the brain. We engineered a brain-machine interface that captures neuronal signals from an early stage of olfactory processing in awake mice, and used machine learning techniques to form a sensitive and selective chemical detector. We chronically implanted a grid electrode array on the surface of the mouse olfactory bulb and systematically recorded responses to a large battery of odorants and odorant mixtures across a wide range of concentrations. The bio-electronic nose has a comparable sensitivity to the trained animal and can detect odors on a variable background. We also introduce a novel genetic engineering approach designed to improve the sensitivity of our bio-electronic nose for specific chemical targets. Our bio-electronic nose outperforms current detection methods and unlocks a wide spectrum of civil, medical and environmental applications.

bioengineering↗

bioRxiv2019

Mechanical matching of implant to host minimises foreign body reaction

Medical implants offer a unique and powerful therapeutic approach in many areas of medicine. However, their lifetime is often limited as they may cause a foreign body reaction (FBR) leading to their encapsulation by scar tissue1-4. Despite the importance of this process, how cells recognise implanted materials is still poorly understood5, 6. Here, we show how the mechanical mismatch between implants and host tissue leads to FBR. Fibroblasts and macrophages, which are both crucially involved in mediating FBR, became activated when cultured on materials just above the stiffness of healthy tissue. Coating stiff implants with a thin layer of hydrogel or silicone with a tissue-like elastic modulus ([~]20 kPa in subcutaneous and [~]2 kPa in peripheral nerve implants) or softer significantly reduced inflammation and fibrosis three months after implantation. Materials stiffer than the host tissue led to nuclear localisation of the mechanosensitive transcriptional regulator YAP in neighbouring cells in vivo, confirming mechanotransduction. The alleviation of FBR by soft coatings not exceeding the stiffness of the host tissue provides a strategy to achieve long-term implant stability without extensive modification of current implant manufacturing techniques, facilitating clinical translation.

bioengineering↗

bioRxiv2018

NeuroRoots, a bio-inspired, seamless Brain Machine Interface device for long-term recording.

Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.\n\nIn this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10{micro}m wide, 1.5{micro}m thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35{micro}m microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology rigs and with measurements of interests in behavioral experiments in adult rats freely moving into maze. We demonstrated that NeuroRoots electrodes reliably detected action potentials for at least 7 weeks and the signal amplitude and shape remained relatively constant during long-term implantation.\n\nThis research represents a step forward in the direction of developing the next generation of seamless brain-machine interface to study and modulate the activities of specific sub-populations of neurons, and to develop therapies for a plethora of neurological diseases.

neuroscience↗