Neurological conditions affect nearly one in six people in the world, imposing significant health, economic and societal burden. Bioelectronic medicine aims to restore or replace neurological function with the help of implantable electronic devices. Unfortunately, significant technological limitations prohibit these devices from reaching patients at scale, as implants are bulky, require invasive implantation procedures, elicit a pronounced foreign body response, and show poor treatment specificity and off-target effects. Over the past decade, new devices made using methods from microelectronics industry have been shown to overcome these limitations. Recent literature provides powerful demonstrations of thin film implants that are miniaturised, ultra-conformal, stretchable, multiplexed, integrated with different sensors and actuators, bioresorbable, and minimally invasive. I will discuss the state-of-the-art of these new technologies, with emphasis on ultraflexible cortical interfaces for the brain, spinal cord and perispheral nerves. I will also discuss barriers that need to be overcome for these technologies to reach patients at scale.

Neural probes that contain microelectrode arrays are employed as tools to understand better the intricate networks in the nervous system by recording neural activity in the form of action potentials and local field potentials, as well as therapeutic approaches to treat and restore lost sensorimotor functions via neuromodulation, for example, electrical stimulation. Nonetheless, the implementation of devices that match the three-dimensional (3D) topology of nervous tissues is still challenging. Aiming to capture and interact with neural activity from single to groups of neurons in the 3D space of nervous tissues, this work presents the development and implementation of fully flexible multisite 3D penetrating neural probes (NPs) for in vitro and in vivo neural applications.

Combining thin film technology and surface micromachining processes with two-photon lithography (2PL), we developed 3D-printed NPs based on self-aligned template-assisted electrodeposition processes [1]; Kiri-NPs based on two-dimensional (2D) designs followed by a kirigami cut-and-fold approach; and 3D NP-stacks, based on the stacking of 2D NPs with key-lock systems. Furthermore, we optimized the cross-sectional dimensions to reduce the bending stiffness of the penetrating probes, thereby allowing the implementation of an atraumatic insertion by reducing the effective length of the penetrating shanks of the NPs.

Exploring the scope of our 3D neurotechnology, we tested the NPs in different neuronal models, spanning from explanted rodent retinas and human brain slices in vitro to the cortex of rodents in vivo. While all three devices enabled 3D laminar recordings across neural models capturing both single units and neuronal population activity, 3D-printed NPs, and Kiri-NPs simultaneously allowed the additional recording of neuronal potentials from the tissue surface. On the other hand, 3D NP-stacks promise access to deeper neural structures, by facilitating the implementation of additional insertion aids, such as dissolvable polymer braces.

Achieving an aspect ratio of 3D microelectrodes of up to 33:1, multiple multisite shanks up to 128 shanks in a standalone device, and a density of 44 shanks/mm², 3D-printed NPs, Kiri-NPs, and 3D NP-stacks, respectively, comprise a pool of 3D neurotechnologies that is highly customizable and adaptable to the anatomy of different neural structures. Hence, these technologies hold the potential of easily increasing the topological dimensionality of neuroelectronic interfaces to address single or groups of neurons, to networks across neural layers and regions. The deployment of such technology is then versatile, from the investigation of micro-seizures in epileptic models in vitro to the further development of visual prostheses to enable a bidirectional communication for the simultaneous recording and stimulation of the visual pathway [2], [3].

State of the art implantable bioelectronics for health and research applications require
improvement. The major challenges include: 1) tethered connections for animal monitoring are
prone to infection and induce stress; 2) wireless solutions for human use rely on batteries,
occupying up to 90% of the device volume. Wirelessly powered/rechargeable options often rely
on large subcutaneous modules, necessitating complex surgeries for implementation.
Our vision aims to enable wireless and battery-less bioelectronic devices, making them extremely
miniaturizable and long-lasting, paving the way to less invasive injectable bioelectronics,
facilitating the use of soft and deployable devices, surgical micro-robotics, and ultra-miniature
biosensors. To achieve this, we bridge recent advancements in three disciplines: the physics of
wave control in complex media, conformal reconfigurable radiating surfaces, and implantable
electromagnetic structures. Our work investigates the physical mechanisms governing the
radiation efficiency of implantable bioelectronic devices deep within human body tissues. Based
on our findings, we have developed and implemented novel electromagnetic structures. Our
models identify key parameters and their quantitative relationships in various scenarios, enabling
the calculation of specific electromagnetic design rules tailored to each application (e.g.,
electromagnetic source type, operating frequency, dimensions, material properties). Our results
demonstrate that the wireless performance of bioelectronics can be enhanced by a factor of five
to ten in terms of radiation efficiency compared to conventional designs. This breakthrough has
the potential to reshape biomedical research, leading to more effective treatments and providing
valuable tools for researchers

Over the past twenty years, nanoscience has advanced rapidly, leading to significant developments not only in materials science and physics, but also impacting various fields from life sciences to engineering. Among these advances, micro- and nanoelectrodes ranging from micron to sub-micron in size, have been particularly important in neurosciences, where they are the primary functional elements of neuroelectronic devices designed for recording and electrical stimulation. Here we report on improvements in electrode fabrication and design, and the integration of nanoelectrodes with microelectrodes. In addition, as electrode dimensions decrease, new electrostatic and electrochemical effects emerge that enhance intracellular sensing applications. In particular, tight physical coupling between the electrode and the neuron leads to higher signal-to-noise ratio (SNR) of extracellular recordings due to better isolation of the electrode from noise, and recent applications of high aspect ratio nanostructures for neural applications show substantial passive improvement of extracellular recordings [1]. Tight cell-electrode coupling relies on the reorganization of structural proteins within the cell, but the details of the mechanisms behind this reorganization are not fully understood [2], hindering the design of an ideal structure for high SNR passive recordings.

In this study we push cell-electrode coupling in the nanoscale through the engineering of high-aspect ratio nanopillars with diameters below 100nm. These nanostructures allow us to uniquely probe neurons as they approach the diameter of curvature of sub-cellular features. These sub-cellular nanopillars are then integrated onto micro electrode arrays (MEAs) and in high-density large-scale arrays to investigate the neurons through a range of experiments. The fabrication of the nanopillars utilizes the nanometer resolution of electron beam lithography (EBL) combined with the conformality of atomic-layer deposition (ALD).

To investigate the cell-chip coupling, E18 rat cortical neurons were cultured on the nanopillars on different platforms. The physical and structural characteristics were investigated through critical point drying (CPD), focused ion beam (FIB) milling of ultra-thin plasticization (UTP) [3] preserved cells, and immunostaining. Whereas, the electrophysiological coupling was explored through nanopillar MEA recording with simultaneous patch clamp.

To better understand the brain and better treat brain disorders, it needs to be neuromodulated targeting multiple areas of the interacting brain networks using ‘brain-like’ waveforms [1]. Moreover, these waveforms need to be applied in a smart way, based on feedback and in a closed-loop fashion. This requires sensing technology, not only for reading the electro-chemical signalling of the brain itself but also of other physiological parameters. Additionally, this feedback needs to be self-learning so it can learn to recognize the (personal) brain activity and connectivity characteristics that characterize a symptom and the intensity of a symptom. It then selects an optimal stimulation design to normalize the symptom by increasing or decreasing connectivity to change the network structure.

This talk will address how these ‘NeuroDots’ can do this, what they will look like, and which future developments are needed to make them a reality. In particular, we will look into the network organization of the brain, the NeuroDots technical requirements, implant configurations, and new modalities to interact with our electro-chemical mainframe to truly feel better.

In this work, we introduce a novel nerve-on-a-chip model designed as a neural interface for deep brain stimulation. Termed as a "biohybrid" approach, it aims to overcome the limitations of standard deep brain implants such as low stimulation resolution. The biohybrid concept leverages on-chip grown retinal neurons to convert electrical signals from a stretchable 2D microelectrode array into synaptic stimulation of a neural target tissue.

The device consists of two primary components: a soft, stretchable multi-electrode array (MEA) and an axon-guiding microstructure [1]. The MEA, fabricated using a transfer stripping method [2], comprises a PDMS substrate and microstructured platinum tracks. The PDMS microfluidic axon guidance structure is aligned and bonded onto the microelectrode array. Spheroids of living retinal neurons labelled with a viral vector (mRuby3) are then seeded into 16 seeding wells and cultured under standard cell culture conditions before implantation.

We describe the fabrication of the biohybrid neural interface and characterize the device electrically and mechanically. We demonstrate how the retinal ganglion cells seeded into the implant form an artificial nerve of up to 3 mm in length. Moreover, we demonstrate how axons transit from the biohybrid implant into a nerve-forming bioresorbable collagen tube that will guide axons from the implant towards a neural target structure for sensory reinnervation and synaptic stimulation of the visual thalamus in vivo. We show that retinal spheroids can be stimulated using the stretchable microelectrode array using functional calcium imaging. To assess stimulation-induced signal transmission in the biohybrid implant we present in vitro data on how spikes propagate within the axon guidance channels using CMOS [3] multielectrode arrays. Lastly, we demonstrate that neurons cultured in the device grow axons in the microstructure, and exhibit spontaneous activity for over 3 weeks when implanted in mice.

With this work, we show that this biohybrid approach has the potential to serve as a new kind of neural interface technology. Although further experiments are necessary for in vivo synapse formation and deep-brain stimulation, previous work has show feasibility of this approach in vitro [4], and the findings presented in this work pave the way for a new kind of neural interfaces.

Low delivery efficiency and toxicity of many chemotherapeutics limit their effectiveness in cancer treatment. Local chemotherapy is an approach to increase the effectiveness of cancer treatment. To enable not only spatial, but also temporal control of drug delivery, we utilize iontronic pumps (IPs). Drug delivery with IPs is achieved by electrophoretic transport of ions through ion-exchange membranes (IEM).¹ IEMs consist of crosslinked networks of charged polymers that block transport of oppositely charged compounds. Important requirements for IEMs are ion-selectivity and passive leakage prevention. In case of ion-selective and low leakage IPs, electronic current corresponds to the ionic delivery current, thus providing a drug delivery platform with high dosage control. However, IP drug delivery is limited to low Mw and charged compounds, making it unsuitable for delivery of large or uncharged drugs.² To expand the drug library with large and uncharged drugs, we envision the delivery of a small trigger for the release of potent chemotherapeutics via a bioorthogonal click-to-release mechanism. Ligation of the potent chemotherapeutics onto a hydrogel, located at the tumor site, ensures local release and high concentration of the drug and the bioorthogonal approach reduces side effects. Our goal is to control drug concentration profiles at the tumor site, which opens op avenues for spatiotemporally controlled administration of highly potent chemotherapeutics, without the need for systemic administration of (pro)drugs or drug conjugates.

Treatment of glioblastoma multiforme (GBM) is highly challenging, with current treatments—surgery, chemotherapy, and radiotherapy—yielding a median survival of just ~15 months. The blood-brain barrier (BBB), a semipermeable membrane, complicates drug delivery by blocking potent chemotherapeutic agents from reaching the tumor. This barrier, along with other factors, necessitates innovative approaches to brain cancer treatment. Iontronic pumps (IPs) have emerged as a promising solution. These devices use an ion exchange membrane to precisely control drug release, potentially overcoming the BBB's limitations.

After encouraging results from previous in vitro and in vivo studies, we have now established the operation of IPs in a rat brain tumor model. Utilizing a semi-wireless, Bluetooth-controlled setup, we aim to conduct long-term studies on awake rats. We induce brain tumor growth via a catheter system, through which our device is then inserted for operation. To assess the efficacy within the tissue, we have established protocols to evaluate tumor size, molecular expression of different markers, and pharmacokinetic drug distribution. These experiments aim to evaluate the efficacy of continuous drug dosing in targeting difficult-to-treat tumors over extended periods, taking the chemotherapeutic potential of IPs to the next level.

Introducing an innovative monitoring system designed to evaluate surface modification by thin molecular layers, this technology integrates Surface Plasmon Resonance (SPR) with electronic detection via Organic Field-Effect Transistor (OFET) technology. Central to the system is an Extended Gate OTFT (EG-OTFT) configuration that includes a nanostructured component for surface plasmon resonant excitation. This unique device structure not only reliably detects layer-by-layer deposition of various polymers, akin to traditional SPR, but also uniquely discerns between positively and negatively charged layers due to the EG-OTFT's detection capabilities. This dual functionality significantly enhances the system's bioanalytic measurement potential. The combination of optical and electronic detection offers versatility and heightened sensitivity, marking a substantial advancement in biosensing technology. This system provides a cost-effective, reliable, and detailed analysis of surface modifications, crucial for diverse scientific and industrial applications, from biomedical diagnostics to environmental monitoring. This development ushers in more accessible and efficient monitoring platforms tailored to the evolving demands of modern research and applications.

Action Potentials (APs) of excitable cells like cardiac cells, skeletal muscle cells and neurons encode crucial information about the cells physiology and physiological state. Most of electrical tools available at present to probe APs are either invasive or require complex manufacturing processes. Minimally invasive and high-throughput recording of intracellular action potentials in electrogenic cells with scalable technologies is in high demand. With the aim of enabling a cost-effective, non-invasive probing platform based on devices that can be easily fabricated and processed from solution with large-area printing techniques, we propose planar Electrolyte Gated Field-Effect Transistors (EGFETs) based on printed polymer semiconductors. Remarkably, despite the planar geometry of the device, we could demonstrate the spontaneous recording of intracellular APs of human induced pluripotent stem cells derived cardiomyocytes. The simplicity of the device combined with the high signal to noise ratio opens up new opportunities for low-cost, reliable, and flexible biosensors and arrays for high quality parallel recording of cellular action potentials.

The organic electrochemical transistor (OECT) is an exciting device at the forefront of bioelectronics, with applications ranging from biosensors, electrophysiological monitoring, circuits, etc.

OECT operation and performance rely on the properties of its core components – a mixed ionic/electronic conductor in contact with an electrolyte – and on the form factor that is imparted during device fabrication.¹ While tremendous efforts have been done to improve device performance, strategies that combine efficient operation and sustainable design are still lacking. Most organic mixed ionic/electronic conductors are synthesized using multiple steps involving toxic precursors, expensive transition metal catalysts, and repeated purification steps. OECT microfabrication is mostly performed using cleanroom-based photolithography, hindering fast prototyping and widespread adoption of this technology for low-volume, low-cost applications.

To enable the transition from the laboratory to usable products, materials need to be cheap, scalable, and free from toxic precursors. Fabrication methods should enable high resolution while being affordable and allowing rapid prototyping. Here, I will discuss two of our recent works aimed at addressing these challenges.

From the materials perspective, I will show that blending a n-type conjugated polymer p(N-T) with large amounts of insulating commodity polymers (six times more) can improve OECT performance while drastically decreasing the amount of conjugated polymer used in the blend.^2,3 We found that the improvement in μC* is due to a dramatic increase in electronic mobility by two orders of magnitude, from 0.059 to 1.3 cm² V^-1 s^-1 for p(N-T):Polystyrene 10KDa 1:6. Moreover, devices made with this polymer blend show better stability, retaining 77% of the initial drain current after 60 minutes operation in contrast to 12% for pristine p(N-T). Moreover, I will present a scalable method based on cleanroom-free polymer patterning for OECT fabrication using ultrafast focused laser exposure.⁴ This approach enabled micrometer resolution in OECT fabrication while cutting down on the steps needed with conventional manufacturing using photolithography. The utility of this OECT manufacturing approach was demonstrated by fabricating complementary logic (inverters) and glucose biosensors, thereby showing its potential to accelerate OECT research.

The development of multifunctional organic materials represents a vibrant area of research, with applications spanning from biosensing to drug delivery.^[1,2] This study shows the development of a multifunctional bioelectronic device suitable for prolonged temperature monitoring and drug delivery applications. The device relies on a conducting and thermo-responsive hydrogel made of poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) and poly(N-isopropylacrylamide) (PNIPAM). This multifunctional hydrogel is 4D printable by Digital Light Processing (DLP) method and exhibits optimal biocompatibility. The hydrogel features a low critical solution temperature (LCST) ≈ 35 °C, above which its resistance changes dramatically due to the shrinkage it undergoes with temperature. The integration of PNIPAM/PEDOT hydrogel into an organic electrochemical transistor (OECT) as the gate electrode allows to generate a miniaturized bioelectronic device with a reversible response to temperature variations between 25 to 45 °C, along with high sensitivity of 0.05 °C⁻¹. Furthermore, the PNIPAM/PEDOT hydrogel demonstrates its utility in drug delivery, achieving an Insulin-FITC release rate of 82 ± 4 % at 37 °C, mimicking human body conditions. The hydrogel’s functionality to store and release the insulin does not compromise its thermo-responsivity and the overall performance of the OECT. This multifunctional OECT opens new avenues for the development of customizable and personalized sensing and drug-delivery systems.

DOI:  https://doi.org/10.1002/adfm.202403708

Cardiomyocytes differentiated from pluripotent stem cells (PSC-CMs) hold a great potential for the study and the cure of cardiovascular disease; indeed they have been extensively used as platform for disease modeling and drugs testing, and represent a promising source of cells for regenerative therapies. However, the immature phenotype of these cells, which differ from adult cardiomyocytes for molecular, metabolic and morpho-functional properties, is a major hurdle for their full application. Recently, a new technology based on optical excitation of light-sensitive organic semiconductors (OS) has been shown to be able to modulate cell behavior of many cell types by targeting different cellular pathways, as proliferation, angiogenesis, neuronal firing and contractility. Here, we adopted a multidisciplinary approach based on morpho-functional, metabolic and transcriptional analyses to investigate the effect of OS-photoexcitation on PSC-CMs. Analyses were performed on PSC-CMs seeded on either glass (control) or a red-light sensitive OS polymer namely Poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-bʹ]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT), in form of a thin film. Our results revealed a significant modulation of markers of CM maturation in PSC-CMs exposed to PCPDTBT and photomodulation, showing an increased size, by means of membrane capacitance, a shift of their maximal diastolic potential (MDP) toward more negative values, and augmented Ca²⁺ transient amplitude. Moreover, by Scanning ElectroChemical Microscopy (SECM) we found a decrease in glucose uptake and lactate release upon PCPDTBT light stimulation, potentially indicating a switch toward a more adult-like metabolism in stimulated PSC-CMs. Recently obtained RNA sequencing data are in line with these results, and will provide us with hints on the underlying molecular mechanisms. In conclusion, although not  definitive, our data are in support of a potential effect of polymer-mediated optical photoexcitation in boosting PSC-CMs toward a more mature phenotype. The demonstration of a relevant effect of OS-photomodulation on PSC-CM maturation and functionality will significantly promote their full applications toward personalized medicine.

Two-way communication between electronics and neural tissue is key for advancing diagnosis and therapies for neurological diseases and disorders. Establishing such neural interfaces is a major challenge, as the tissue response to implants can have a detrimental effect on the signal quality and functionality of the implant. Matching of the mechanical properties of the electronic implant to the soft interfaced tissue can reduce the tissue response and improve the long-term performance of the device. This requires soft and stretchable conductors, which typically are composed of elastomer/hydrogels and conductive fillers. However, the tough materials requirements on biomedical implants, including material chemistry, mechanical and electromechanical properties, and long-term stability, disqualifies most of the developed stretchable electronic materials for such applications. Here I will present our efforts in developing inert soft neural electrodes based on stretchable gold nanowire composites. Aspects ranging from nanomaterial synthesis, surface modifications and composite formulations to laser fabrication, device design and characterization will be covered. The performance of the soft electrodes in vivo will be discussed together with future challenges and opportunities.

www.liu.se/en/research/soft-electronics

Among the many molecules tested every years as potential drugs, 90% fail to reach the market despite sometimes more than 12 years of development and over two billion individual cost. As rejections are often related to cardiovascular issues, some cell-lines such as hiPSC cardiomyocytes have been extensively used to model drug toxicity in vitro, translating efficiently to clinical trials afterward. However, at the current state of art, parameters such as mechanical contractility, electrophysiological signals and calcium fluxes have to be measured separately, on different types of device and often on different in vitro cultures. This makes the interpretation of results difficult and therefore reduce their relevancy.  In that context, we developed a novel device that: i) is able to optically record electrophysiological signals in a label-free and non-invasive manner. ii) has embedded electrodes for direct recordings of field potentials and for cell stimulation at the electrode location iii) is transparent enough to enable calcium imaging using fluorescence microscopy. Moving beyond the simple sum of these data , the device couples these modes that can be used independently and simultaneously. Thus, it provides a platform on which relevant and time-efficient studies of cardiotoxicity can be performed. One can use electrodes to pace the surrounding cells and detect discrepancies in cardiac frequency due to assayed drugs. The cardiotoxic effect can be detected at the whole culture level using the high density optical sensors.  In this work, we could observe for example the respective increase and reduction in action potential duration using E-4031 and Nifedipine drugs. To conclude, this device exploits and combines microfluidics, fluorescent dyes, complex nanofabrication and pass-through electrodes to transduce the cardiac action potentials into optical signals. Using the same structure, it can also perform basic electrical recordings and stimulation, allowing deep studies of drugs cardiotoxicity, necessary to improve drug approval rates.

Electrolyte Gated Field-Effect Transistors (EGFETs) based on conjugated polymers have emerged as fundamental building blocks in bioelectronics due to their ability to convert weak biological signals into amplified electronic outputs while operating stably in aqueous environment. Conjugated polymers exhibit biocompatibility and ‘soft’ mechanical property thus favouring direct coupling with biological cells, tissues and organs. As such, EGFETs have been used for monitoring cell cultures and for electrophysiological recording of excitable cells such as neurons and cardiac cells. In such applications, cells are directly plated onto the active channel of the transistor that is comprising of an organic polymer coated with a porous protein to enhance cell adhesion. Therefore, ion fluxes due to the electrical activity of the cell such as the Action Potential (AP) is directly coupled to the EGFET resulting in a modulation of the channel conductivity that is measured in transistor current modulation. While it is true that the amplification factor of EGFET has to be maximized to provide large local amplification of the bio- signals, recording the accurate signal of the action potential however goes beyond the device intrinsic electrical parameters. In this context, I will present our latest results where we employed an EGFET made of different conjugated polymers to record the action potential of a 2D layer of human induced Pluripotent Stem Cell-derived Cardiomyocytes (hiPSC-CMs). Interestingly, we observed that depending on the active polymer employed as active channel for the EGFET, the recorded AP has the shape of either an intracellular –like or a Field Potential (FP) as recorded using simple microelectrodes. Surprisingly, an EGFET with a much lower transconductance could transduce the AP signals much more accurately than an EGFET with a large transconductance. This indicates that the electrical coupling between the cell and the transistor channel predominantly relies on the interface between the cell membrane and the polymer at the cleft.

The ability to interact with electrogenic cells and to monitor their status plays a pivotal role in neuroscience, pharmacology and cell biology. We deeply investigated both theoretically and experimentally the interactions of nanostructured surface sensors with living cells such human neurons and cardiomyocytes. The aim is to make an effective interface between the intracellular compartment and different class of nano-sensors including optical sensors for plasmonic enhanced spectroscopies, nanostructured electrodes for electrical measurements and, nano-needles for intracellular delivery or sampling [1,2,3]. In this talk we will revise our strategy to sense intracellular activities with a focus on electrical activities. In this regard, we developed a method for opening transient nanopores into the cell membrane with no side effect [1]. After the membrane poration the tip of the sensor is in direct contact with the intracellular compartment thus enabling intracellular investigations which include Raman traces of biomolecules, electrical recording of action potentials of human neurons and cardiomyocytes. We demonstrated the possibility of non-invasively testing the effect of relevant drugs on human cells with particular regard of cardio-toxicity that is a fundamental step before the clinical trials [4,5]. Still in this context, we introduced a radically new concept for monitoring action potentials. It bases on the concept of “mirror charge” in classical electrodynamics (figure 1): electric charges placed in proximity of a conductor affect its spatial charge distribution thus generating mirror charges into the conductor itself. Hence, by monitoring the dynamics of the mirror charges one can monitor the dynamics of the “source charges” and the related electric potential, i.e. the action potential [6,7,8]. However, being the dyes placed in microfluidic chip, separated from the cell culture, the cells are subjected neither to dye contact, nor to direct light illumination, but are in a perfectly unperturbed physiological state. Remarkably, the optical signal perfectly resembles an action potential even without the need of cell membrane poration as for conventional electrical recording.

The replication of neural information processing in electrical devices has been extensively studied over the years. The paradigm of parallel computing, which allows information to be simultaneously detected, processed, and stored, is required for numerous applications in many fields. In the case of brain-computer interfaces, another important requirement is the suitability of the device for communication with cells. Organic electrochemical transistors (OECTs) based on PEDOT:PSS are used for this purpose due to their ionic-to-electronic signal transduction and biocompatibility. Many works have demonstrated the reproduction of neural plasticity mechanisms, such as short-term facilitation and long-term potentiation. In each device, the physical mechanism of transduction may be different, but it is known that the electrolyte plays a key role in the functioning of these devices, as it provides the ions responsible for the chemical transmission of information. Focusing on long-term memory, this can be reproduced in the OECTs with the oxidation of the neurotransmitter, as in the case of the biohybrid synapse. It is crucial to understand the influence of the material chemistry, electrolyte composition and neurotransmitter-mediated memory effect of the device, as long-term modulation is based on a change in the ionic balance between the electrolyte and the organic polymer.

This electrolyte composition (i.e., bioegel) and neurotransmitter-dependency plasticity will be discussed also to consider the use of neuromorphic OECTs to be interfaced with living neurons to establish biohybrid synapses and neuronal networks. In fact, neurohybrid interfaces can be achieved through bidirectional closed loop communication with various neurotransmitters such us dopamine and glutamate.

Furthermore, I will discuss how conjugated polymers can be engineered with azopolymers (opto-sensitive polymers which switch from cis to trans conformation upon certain light exposure) to feature diverse optoelectronic short- and long-term plasticity, enabling the use of creating functional biointerfaces with living neurons. In fact, conductive polymers and light-sensitive surface coating can also enable electromechanical coupling with neuronal cells, enhancing the cell-chip coupling at different scales. These biomimetic materials will enable a new class of bioelectronic device used for neuronal interfaces towards their application in implantable probes.

Organic conductive polymers offer an ideal solution for interfacing with biological systems due to their unique capacity to transport both electronic and ionic charges, along with mechanical properties that align with those of tissues and cells. They represent a promising avenue for therapeutic innovation, potentially addressing the challenge of remodulating neural circuits and signaling in neurological diseases. When incorporated into cell membranes can produce a remodeling of the membrane properties, and if directly synthesized in living tissues, reduce impedance.[1-3]

Here we utilize the capability of bis-ethylenedioxythiophene-thiophene (ETE) monomers to be enzymatically polymerized in situ,[4] to create, through non- covalent interactions, seamless interfaces between conductive polymers and lipid membranes, in both synthetic models and living cells. [5, manuscript in preparation] A variety of experimental techniques is employed to examine both the morphological and electrical properties of these interfaces and the impact of the assembled polymer on cell behavior.

These findings suggest that these materials have the potential to serve as the foundation for innovative strategies for in vivo neural therapeutics, while also broadening our comprehension of the emerging field of in situ-fabricated bioelectronics.

In the last few decades, reactive oxygen species (ROS) have emerged as a highly powerful cell-signaling agent in disease but also in physiology. ROS effect can vary from detrimental with harmful effects on cell viability to highly beneficial in most biological processes, including cell differentiation, proliferation, and migration, up to specific functionality.^[1] The controlled production of ROS through exogenous stimuli such as light is expected to provide lower invasiveness, relying on wireless stimulation, reversibility, and high spatial selectivity. Semiconducting polymers, originally used in organic electronics, are attracting increasing attention as phototriggers of ROS due to their biocompatibility, intrinsic conductivity and optical properties. For such a purpose, semiconducting polymers are usually processed in the form of thin films and nanoparticles whose performance is influenced by the π-conjugated semiconducting polymer structure and its 3D confinement during the nanomaterial formation. All those features clearly modulate the photophysical processes and ultimately determine their biophotonic applications. However, its application is still limited by its low efficacy and the use of bare photoexcitation does not allow for the necessary fine-tuning of ROS concentration at safe regimes for photostimulation.^{[2, 3]}

To overcome these limitations, we developed porous poly(3-hexylthiophene) (P3HT) films (PSFs) and nanoparticles (PSNPs) with an enlarged surface area (S_a) that allowed to increase the optical absorption surface area, providing easier access to optical excitation for (bio-opto)electronic applications. To that aim, opto-active, electro-active, and hydrolysable graft copolymers were synthesized through chemical oxidative polymerization of P3HT and polylactic acid (PLA), P3HT-g-PLA, with different PLA percentages to tune the pore size. The morphology and pores of PNFs were characterized by Atomic Force Microscopy (AFM) and grazing incidence small angle X-ray scattering (GISAXS), whereas the PSPNs formation and distribution were analyzed by Scanning Electron Microscopy (SEM), dynamic light scattering (~100 nm), and small angle X-ray scattering (SAXS). The PLA hydrolysis was also corroborated by Nuclear Magnetic Resonance (¹H-NMR). The optical properties of the nanomaterials were determined by UV-vis absorption and fluorescence emission spectrophotometry. Finally, the photo-electrochemical properties were determined by irradiating the nanomaterials, immersed in an aqueous physiological electrolyte, with a laser diode. Porous nanomaterials gave rise to a 4-fold increase in the photocurrent properties as compared with non-porous ones, proving enhanced opto-electronic properties of our nanomaterials. The employment of these porous nanomaterials as biophotonic devices for extracellular (PNFs) and intracellular (PSNPs) stimulations of human umbilical vein endothelial cells (HUVECs) allowed us to modulate the ROS production in the beneficial physiological range, up to 6 mW/cm² (λ = 530 nm) in the case of PSNPs, to favor tissue regeneration processes.^{[4, 5]}

Many cancer treatments face challenges due to inefficient delivery and systemic toxicity. Our solution involves utilizing iontronic devices for localized chemotherapy. These devices enable precise and continuous delivery of anti-cancer agents, and therefore, very potent tumor killing properties.

We demonstrate their effectiveness in two ways: i) electrically controlled chemotherapy and ii) releasing potent chemotherapeutics from a hydrogel with an electric trigger. Iontronic chemotherapy was able to stop tumor growth of brain tumors grown in an embryonic avian model. We currently test a wireless iontronic implant in freely moving rats with orthotopic tumors in their brain and monitor the tumor size with MRI.

For using even more potent drugs with efficiencies in the picomolar range, we use a click-to-release mechanism to release drugs from hydrogels, and demonstrate the system with pancreatic cancer cells. This system allows tight control over the release of highly potent therapeutics on demand, ensuring high toxicity specifically towards tumor cells but a non-toxic state when the gel is not activated.

An array of different thiophene-based trimers has been synthesized that combines electronic, chemical, and pharmaceutical functions. These electro-active pharma-materials (e-NP) have been applied onto and into various cell and tissue systems to form seamless bioelectronics that is amalgamated with biology. Selectivity to specific biological components and structures enables us to form well-defined electroactive structures and devices that promise for radically new tools to record and stimulate biological functions, such as neuro-signaling.

In addition, we have developed the organic electronic ion pump that enables the translation of electronic addressing signals into the delivery of bio-relevant ions and charged biomolecules. The OEIP has been developed into different form factors to enable stimulation and therapy targeting a range of neuro-related disorders and diseases.

The objective with the e-NP and the OIEP bioelectronic techniques is to provide minimal invasiveness and selective signal translation at the biology-technology interface.

The fundamentals of, and the results from applications, of the e-NP and OEIP technologies will be reported and discussed.

The union of bioelectronics with engineered mammalian cells is a transformative opportunity in regulated, personalized therapeutics. This approach involves combining the strengths of synthetic biology – namely biological specificity that leverages the natural machinery of cells – with bioelectronic systems, which offer precision timing, dose control, and communication with established sensing technologies and clinical feedback. To this end, we show how implanted biohybrid devices rely on bioelectronics to initiate the production of native peptides, control therapeutic dose, and support the health and productivity of these “cell factories”. We demonstrate optogenetic induction of drug production, the potential for fluorescence feedback via photometry to probe cell factory viability, and on-site electrocatalytic oxygenation for maintenance of implanted cell health at high cell density. Current efforts focus on regulation of circadian rhythms; however, the biohybrid cell therapy concept can be broadly applied to multiple diseases where precision timing and responsive dosing is critical for effective therapy, including Type I diabetes, obesity, and cancer immunotherapies.

Therapy for peripheral nerve and spinal cord injuries as well as several neurodegenerative diseases remain a big clinical challenge due to poor regeneration of neural tissue in the damaged area. [1]. Within this context, human induced pluripotent stem cells  (hiPSC)-derived neuronal networks present an effective in-vitro model for the study of these physiological issues. However, the differentiation and maturation of hiPSCs is a complex and time-consuming process, thereby necessitating techniques for real-time monitoring of neuronal differentiation and maturation with high sensitivity.

Moreover, physical microenvironmental cues, such as electrical signals, have been increasingly recognized as crucial in regulating stem cell behaviour and fate as well as neuron regeneration processes [2]. However, the underlying molecular mechanism demand further investigation [3]. Furthermore, PEDOT: PSS based electrodes have been shown to lower the electrochemical impedance leading to an increased SNR [4] while recording in addition to promoting neurogenic differentiation [5].

In this work, we first designed a microelectrode array and compared the SNR, electrochemical stability, charge storage capacity and charge injection limit of different electrode materials, viz-a-viz, Gold, Gold/PEDOT: PSS and PEDOT: PSS only via Electrochemical Impedance Spectroscopy (EIS), Voltage Transients and Cyclic Voltammetry (CV) measurements.  This is followed by comparison of different electrode designs including inter-digitated, castellated and matrix based. The best electrode designs were used to monitor proliferation of (hiPSCs) followed by the differentiation to cortical neurons with the entire process being analysed by correlating the physiological variations during the process to the variation in impedance magnitude and phase at various frequency bands.

Further studies aim to make the in-vitro platform more biomimetic with flexible mesh-design based electrodes to bridge the dimensional gap between the 3D cultures and the monitoring system.

Neural implants have significantly improved the lives of individuals with spinal cord injuries, Parkinson’s disease, and hearing loss. However, current implants are often large, complex, and invasive, which limits their accessibility. To address this, we are developing injectable and wireless nanoelectrodes made from magnetoelectric materials that are less invasive and risky. These magnetoelectric nanoparticles (MENPs) convert magnetic signals into electrical signals to stimulate nerve tissue without the need for genetic modification [1]. MENPs represent an advanced technology in the field of bioelectronics and hold significant potential for applications such as deep brain stimulation (DBS). They offer a less invasive alternative to traditional methods for modulating neural activity, providing a safer option for patients.

The properties of MENPs are heavily dependent on their surface coatings, which play a crucial role in ensuring their stability, biocompatibility, and functionality. Effective coatings not only prevent the aggregation of nanoparticles, which could impair their function and cause health issues, but also enable targeted control of their interaction with surrounding tissues. Additionally, these coatings minimize immune responses, enhancing the biocompatibility of the nanoparticles and reducing potential side effects [2, 3, 4]

In our study, we coated MENPs with various polymers. Two polymers, oleic acid-polyethylene glycol (OA-PEG) and polylactide-PEG (PLA-PEG), were non-covalently bound to the nanoparticles through hydrophobic interactions. Furthermore, we covalently attached four additional polymers – mPEG, poly(acrylic acid-co-2-acrylamido-2-methyl-1-propane sulfonic acid) (P(AA/AMPS)), polyethyleneimine (PEI), and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) – to our MENPs. We demonstrated that all coatings improve dispersion in liquids and reduce the aggregation of MENPs. Using Dynamic Light Scattering (DLS), we demonstrated that the hydrodynamic diameter of coated nanoparticles is approximately 67% smaller due to reduced aggregation. Absorption measurements of a nanoparticle solution revealed that the coated nanoparticles remain significantly longer in solution before sedimentation compared to uncoated ones. This indicates that the coatings enhance colloidal stability and significantly optimize the behavior of MENPs in liquids. NMR measurements confirmed that the coating adheres firmly to the nanoparticles, as we actively removed the coating and measured the pure polymer amount. Additionally, IR measurements further validated the stability and integrity of the coatings. These results also show that the coatings remain stable at 4°C for over 6 months. We also evaluate the biocompatibility of these coatings to assess their suitability for biomedical applications. All of our PEG-based coatings, including OA-PEG, PLA-PEG, and mPEG, showed no toxicity to human neuronal cells derived from hiPSCs in vitro. Additionally, P(AA/AMPS) and PEDOT:PSS coatings also demonstrated no toxicity at relevant concentrations in vitro. In contrast, only PEI exhibited cytotoxicity, as previously described in other studies [5, 6, 7, 8, 9]. This cytotoxicity could potentially be mitigated in future research by reducing the PEI amount, for example, through the use of a PEI-PEG mixture. These advancements in coating technology enhance the performance and safety of MENPs. By optimizing the interaction between MENPs and biological tissues, these coatings increase the potential for safer, more effective, and less invasive treatments, marking a significant advancement in the field of bioelectronics.

Recording and stimulation using implantable neural implants has been demonstrated as an effective diagnosis and treatment for neurological disorders (i.e. Parkinson’s disease, epilepsy) as well as in neuroprosthesis applications. [1] Conventional devices are fabricated using rigid materials such as metal or silicon which has a significantly higher young’s modulus compared to the neural tissue leading to foreign body reaction (in chronic implantations) due to the mechanical mismatch. [2] Current research in the field is focusing on developing soft and flexible electrodes to better mimic and conform the natural tissue property and reduce the risk of implant rejection. [3] On the other hand, surgical implantation of ultra-soft electrodes to the target location in the brain in a minimally invasive manner remains a challenge. In addition, it is crucial to achieve minimum stab damage during insertion. Therefore, in this project, the goal is to fabricate shuttles using femtosecond laser ablation to facilitate the insertion of ultra-soft neural electrodes at the target site and achieve minimally invasive insertion as well as minimum stab damage to the neural tissue without buckling of the shuttle. Simulations of buckling force is used to optimise the geometry, size and material of the shuttle whereas the laser parameters are optimised for different materials (i.e. tungsten, stainless steel, silicon) to achieve a sharp shuttle tip. The insertion force required to penetrate neural tissue has been previously reported as a relevant metric to assess the extent of caused tissue damage. [4] Here we therefore optimize shuttle geometry, material, and fabrication process to minimize insertion force, which is measured using a motorised micromanipulator on a brain phantom at different insertion speeds. The fabricated shuttles will then be used for the implantation of ultra-soft electrodes.

Human enteric viruses, a diverse array of pathogens recognized for their significant role in global diarrheal disease, pose a considerable public health threat. Their environmental resilience, extensive viral shedding, and transmission via the fecal-oral route underscore the urgency of investigation^[1].

To understand intricate dynamics of viral interactions, elucidate entry mechanisms, and identify anti-viral interventions that impede host entry, the development of in vitro models which faithfully replicate complexities of the gut becomes imperative^[2].

We have engineered a 3D model of the intestine, intricately hosted on a conducting PEDOT:PSS scaffold^[3,4]. This model not only emulates the intestinal epithelial lining more closely than conventional 2D models, but also captures the importance of the lamina propria layer, the connective tissue beneath, which contains important connective proteins and facilitated cellular crosstalk with the overlying epithelium. Monitoring the barrier's integrity over time is achieved through electrochemical impedance spectroscopy (EIS), offering a highly time resolved understanding of the model's response to enteric viruses, including poliovirus-like CVA13.

Our findings reveal the capabilities of our 3D bioelectronic gut models – including sensing virus-induced barrier disruption. We are further aiming to demonstrate electrical monitoring of virus-induced cellular extrusion of epithelial cells demonstrating a novel pathway for viral shedding and disease progression along the intestinal tract^[5]. This approach holds promise in investigating the contraction of diseases and interrupting transmission pathways, which would be a significant stride towards enhanced public health outcomes.

[1]          T.-T. Fong, E. K. Lipp, Microbiology and Molecular Biology Reviews 2005, 69, 357.

[2]          R. McCoy, S. Oldroyd, W. Yang, K. Wang, D. Hoven, D. Bulmer, M. Zilbauer, R. M. Owens, Advanced Science 2023, 2306727.

[3]          C. M. Moysidou, D. C. van Niekerk, V. Stoeger, C. Pitsalidis, L. A. Draper, A. M. Withers, K. Hughes, R. McCoy, R. Acharya, C. Hill, R. M. Owens, Small Science 2024.

[4]          C. Pitsalidis, D. van Niekerk, C.-M. Moysidou, A. J. Boys, A. Withers, R. Vallet, R. M. Owens, Sci Adv 2022, 8, 4761.

[5]          J. Moshiri, A. R. Craven, S. B. Mixon, M. R. Amieva, K. Kirkegaard, Nat Microbiol 2023, 8, 629.

G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors [1]. Their abundance and involvement in numerous physiological processes within the human body, render GPCRs pivotal targets for pharmaceutical intervention, with over one-third of FDA-approved drugs targeting these receptors [2]. While assessing binding characteristics of GPCRs is essential during drug development, common optical assays rely on ligand labelling, which impacts binding characteristics and increases costs [3]. A cost-efficient alternative that forgoes labelling is presented by biomembrane-based bioelectronic sensing techniques, which employ cell-derived membrane models such as native supported lipid bilayers (SLBs) [4].

This work explores the feasibility of investigating GPCR ligand binding within cell-derived membrane models in the form of vesicles (blebs) and SLBs. Blebs and SLBs obtained from two distinct GPCR-expressing cell lines were probed via Nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET) binding assays for GPCR functionality. It was observed that cell-derived vesicles could serve as viable substitutes for intact cells in discerning specific GPCR ligand binding characteristics. Additionally, these vesicles can be used to form native supported lipid bilayers and record characteristic binding behaviour. This means that functional GPCRs can be obtained via a simple chemically induced cell blebbing process and incorporated into native SLBs, representing a meaningful stride towards an electrical detection of GPCR ligand binding.

The integration of such biomembrane-based bioelectronic sensing techniques with microfabricated electronic device arrays presents a promising opportunity for high-throughput screening, with substantial potential to transform drug discovery. Future work will focus on complementary techniques to validate functionality of GPCRs in native SLBs formed from blebs as well as coupling biomembranes to electronic chips to explore the feasibility of electrically investigating GPCR ligand binding.

Seamless integration between biological systems and electrical components is essential for enabling a twinned biochemical-electrical recording and therapy approach to understand and combat neurological disorders. Employing bioelectronic systems made up of conjugated polymers, which have an innate ability to transport both electronic and ionic charges, provides the possibility of such integration. Translating enzymatically polymerised conductive wires, recently demonstrated in plants and simple organism systems, into mammalian models, is of particular interest for the development of next-generation devices that could monitor and modulate neural signals. As a first step toward achieving this goal, enzyme-mediated polymerisation of two thiophene-based monomers was already demonstrated on a synthetic lipid bilayer supported on a Au surface. This study is extended to supported lipid bilayers made up of native lipids derived from cell membranes as the next step in implementing this system in vivo, and to gain further insights into the molecular interactions occuring at the polymer-bilayer interface.

The development of detectors for high energy photons, protons and heavy particles is a long-lasting research topic not only for fundamental applications but also, more recently, for medical applications in radio and hadron therapy. There is an increasing demand for sensors able to provide, ideally in-situ and in real-time, an accurate recording and mapping of the dose delivered during a treatment plan. The development of novel high performing, thin and flexible sensors for the detection of ionizing radiation in real-time at affordable costs is rapidly increasing, as the technology currently available still fails to address the requirements of large-area, conformability and portability, lightweight and low power operation.

Organic small molecules and polymers are promising active layers for advanced dosimetry purposes, as their mechanical features allow the development of devices able to adapt to complex contoured surfaces with outstanding portability (low power operation) and lightweight. They also provide the unique possibility to develop human-tissue-equivalent detectors, thanks to their density and composition, which makes them ideal candidates for medical dosimetry applications. Their low average atomic number and density, also grants a low absorption of the incoming radiation, making them extremely radiation-tolerant. The physical process of radiation detection for organic thin- film based detectors will be discussed in two different configurations: 1) the direct one, based on a simple planar device with an organic thin film as active conversion layer, and 2) the indirect one, based on a polysiloxane-based scintillating layer effectively coupled to an organic phototransistor (OPT).

We report on their performance under exposure to intense photons and MeV protons radiation fields and will discuss how to detect and exploit the energy absorbed both by the organic semiconducting layer and by the plastic substrate, allowing to extrapolate information on the irradiation history of the detector. A new kinetic model has been developed to describe the detector response mechanism, able to precisely reproduce the dynamic response of the device under photon/proton irradiation and to provide further insight into the physical processes controlling its response.

Almost all current understanding of the operation of organic electrochemical transistors is based on the Bernards-Malliaras model published in 2007. [1] The beauty of this model is in its simplicity, and its simplicity suggests that it may not cover all potential scenarios. Using detailed 2D semiconductor device simulations that include the ions’ electrochemistry,[2,3] we produce maps of the charge carriers (electronic & ionic) and electrochemical potential. Using steady state and time domain measurements, we could identify a better set of assumptions needed to generate an analytical model.

Unlike the traditional approach, we do not account explicitly for the ions and use the charge neutrality principle to stay in the electronic domain.

With the aid of the 2D simulations and the improved analytical model, we will present an intuitive description of the OECT operation and discuss issues like the characteristic response time, channel resistance, and the apparent threshold voltage. If time permits we will also address hysteresis effects.

Deep brain stimulation (DBS) is an established neuroelectronic therapy for the treatment of several neurological disorders, including Parkinson's Disease (PD), which is the focus of this work. Current Parkinson's DBS implants, despite their relatively broad clinical adoption, exhibit problems of invasiveness and precision in targeting specific brain regions, which is crucial for maximizing therapeutic benefits while minimizing side effects and lack of focalized and adaptive treatments that can avoid continuous brain stimulation and improve safety over extended periods of time. In this work, we propose the use of microelectrode thin film technology based on reduced graphene oxide, a highly porous material that offers exceptional charge injection and very low impedance, enabling accurate brain recording for biomarker monitoring and focal microstimulation. Our thin film technology consists of 10 µm thin, highly flexible neural leads featuring a high-density array of microelectrodes of 25 µm in diameter.

Experiments were conducted in control and Parkinsonian rats, under anesthesia and in awake state, to investigate specific biomarkers and to evaluate the effect of neuromodulation. Thanks to the recording capabilities of the graphene microelectrodes and its high density, it was possible to precisely localize the subthalamic nucleus (STN), a key structure in Parkinson’s disease, through the recording of single-cell action potentials.  

By comparing PD and control rats, we were to observe a robust increase in neuronal burst activities in the STN of the Parkinsonian rats, which was enabled by the use of microelectrode recordings. Electrical stimulation through those microelectrodes inside the STN induced desynchronization in neuron firing, effectively modulating STN activity to levels comparable to non-Parkinsonian animals.

The stimulation exhibits focal precision, activating an area up to 100 µm away. This allows targeted treatment of small brain regions, such as the STN, without affecting other neural structures. These effects last for several minutes post-stimulation, encouraging the implementation of a closed-loop system to improve therapy efficacy and energy battery consumption. Future studies will be conducted to evaluate the presence of behavioral changes produced in the awake state.

References

Viana, D. et al. Nanoporous graphene-based thin-film microelectrodes for in vivo high-resolution neural recording and stimulation. Nat. Nanotechnol. (2023) doi:10.1038/s41565-023-01570-5.

 Rodríguez-Meana, B. et al. Engineered Graphene Material Improves the Performance of Intraneural Peripheral Nerve Electrodes. Adv. Sci. 2308689, 1–19 (2024).

Organic bioelectronics deals with the study of organic electronic devices which are operating at the interface of biology and electronics. Its applications range from wearable to implantable devices, which e.g., can work as sensitive biomedical sensors. A perfectly suites material for these applications are organic mixed ionic-electronic conductors (OMIECs) as they enable both ionic and electronic transport. Additionally, they feature mechanical flexibility, can be successfully fabricated in versatile processing conditions, and are synthetically tunable.[1] While recent progress in bioelectronics has focused on device fabrication and comparing efficiency of different materials, there is still a lack of a deeper understanding of the fundamental processes occurring in operating OMIECs.[2] Charge transport happens mainly on the π-conjugated backbone of the organic semiconductor, while ions penetrate the bulk material. PBTTT is a polymer with high charge-carrier mobility. The polymer’s performance can be further improved by incorporating alkyl side chains with an ether group to the backbone. This change in polymer structure facilitates the ion uptake in the polymer matrix, hence enhancing the device efficiency.[3, 4] Therefore, in this study we use high temperature rubbing to orient PBTTT-⁸O films helping to unravel the fundamental functioning of both ion and charge transport. For comparison, the same experiments were carried out with an OMIECs workhorse material P3HT, which has already been characterized by multiple different research groups.[5]

Combining electrochemical and chemical doping with spectroscopic techniques and chronoamperometry, we have investigated the oxidation behavior of the OMIECs. In particular, the scattering frequencies of charge carriers in semiconductors were detected with in-situ terahertz (THz) spectroscopy. This method allows us to acquire the intrinsic nanoscale conductivity and short-range mobility of the studied OMIECs, which is not affected by any grain boundaries or electrodes. Thereby the analysis of the complex THz conductivity unveils the overall mobility and density of charges. We were able to obtain high conductivities of more than 1000 Scm^-1 for oriented P3HT and PBTTT-⁸O using different doping methods. With electrochemical doping, conductivities around 1200 Scm^-1 were obtained for both P3HT and PBTTT-⁸O and with chemical doping conductivities of more than 2000 Scm^-1 were obtained. Furthermore, temperature dependent THz measurements were carried out on the chemically doped samples. With this data, band-like transport behavior in PBTTT-⁸O was confirmed, showing the large effect of high in-plane orientation of OMIECs.

Plant electrophysiology, the measurement and study of plants’ electrical signals, reflects plant health status and interactions with environments. Its fast-responsive, systemic, and real-time features and non-invasive measurement make electrophysiology attractive for both fundamental study and practical use in plant health monitoring. However, conventional laboratory techniques for measuring plant electrophysiology signals suffer from poor adhesion with plant surfaces, bulky form factors, or invasiveness, making them nonideal for testing in natural environments, either indoor farms or the field.

In this talk, I will share my work on developing wearable electrophysiology sensors that can conform to complex plant surfaces (e.g., hairy, rough, superhydrophobic) and remain adhesive, while also being safe and inducing minimal impact on plant growth. The conformal adhesive attachment of the sensors on plants makes them resistant to motion artifacts, and the non-invasive wearable form factor promises the potential for real-world deployment outside of laboratories. The pillar for such sensing technology is the design of plant-interfacing materials. I will discuss in detail how material design can help tackle the sensing fidelity challenge on plants. I will also showcase possible applications of this technology in plant health monitoring, environment optimization, and crop breeding. With more scientific and technological breakthroughs, electrophysiology sensors will help tackle many plant-related changes facing humanity, in food security, environment, and biodiversity.

Ongoing discoveries with exoelectrogenic microbes have inspired the latest developments in whole-cell energy devices. This devicees rely on the effective interfacing of living microbes and electrodes for bioelectricity generation. A combination of materials engineering and biological engineering has thusfar contributed to record-breaking device performances in microbial fuel cells and living photovoltaics. These advancements have largely focused on the expression of protein-based electron conduits in bionengineered microbes [1], conductive polymer-based electrodes [2-3] and nanobionics [4] for enhancing device performances.

This presentation focuses on complementary approaches that exploit biosynthetic material characteristics. We explore the development of biosynthesizable electrodes based on biological polymers [5-6] as well as soluble biological mediators [7]. This presentation also examines the development andoptimization of solid-state  electrode constructs with enhanced charge-extraction capabilities. Finally, we discuss recent techniques inspired by synthetic electronic laboratories. These advancements establish new benchmarking techniques fore electrobiological characterization that have been lacking in the field.

Plant electrical signals are mediators of long-distance signaling and correlate with plant movements and responses to stress. Presently, these signals are studied with macro single surface electrodes that cannot resolve signal propagation patterns and integration, thus impeding their decoding and link to function. Unlike conventional extracellular electrodes, multielectrode (MEA) technology records the distribution patterns of electrical activity in cellular networks using a non-invasive, dense array of electrodes embedded in a substrate. The MEA technology is extensively used in brain and cardiac tissue research to decode the brain connectivity and potential propagation patterns in cardiac myocytes respectively. However, for plant electrophysiology the MEA technology remains fairly unexplored. Here we developed a conformable multielectrode array based on organic electronics for large-scale high-resolution plant electrophysiology. The MEA is developed with standard photolithography fabrication techniques, with parylene C as substrate and encapsulation layer resulting in total device thickness as low as 5 micrometers. The MEA is therefore highly conformable to the plant tissue leading to high Signal to Noise Ratio (SNR). With the conformable MEA we performed spatiotemporal mapping of the electrical activity of  the carnivorous plant Dionaea muscipula a.k.a Venus Flytrap (VFT). VFT consists of a bilobed traps having three trigger hairs in each lobe which serve as mechanosensors. When the mechanosensitive hair is deflected, the mechanical stimulus is translated into an action potential (AP), by sensory cells at the base of the hair. Two action potentials (or two touches) in a short period (less than 30 secs) are required to induce closure of the trap.  We found that the AP actively propagates through the tissue with constant speed and without strong directionality. We also found that spontaneously generated APs can originate from unstimulated hairs and that they correlate with trap movement. Finally, we demonstrate that the VFT circuitry can be activated by cells other than the sensory hairs. Our work reveals key properties of the AP and establishes the capacity of organic bioelectronics for resolving plants electrical signaling contributing to the mechanistic understanding of plants long-distance responses.

Flow sensors are crucial in numerous bioelectronics applications, ranging from drug delivery and tracking biofluids like sweat to monitoring cell cultures and more. However, their development is often hindered by complex microfabrication processes, which limit rapid prototyping and cost-effective production for biomedical uses. Additionally, the performance metrics of these sensors under unified biological conditions remain unexplored. In this study, we introduce a versatile and scalable microfabrication technique using a femtosecond laser, achieving ultra-low dimension flow sensors. We systematically evaluated the flow sensing performance across three types of working mechanisms: thermoresistive, piezoresistive, and differential pressure-based sensors, all sharing identical material and resistive geometrical configurations. This study not only benchmarks the technological performance but also provides insights into the device properties essential for high-performance flow sensors. With simplified fabrication processes and direct biological system interfaces, these sensors show great promise for various bioelectronics applications, including blood flow monitoring and controlled drug delivery systems.

Interfacing electronics and biology opens the need for materials having suitable electrical and mechanical properties, as transporting both ions and electrons and soft mechanical properties. Among all materials, organic mixed ionic-electronic conductors (OMIEC), and in particular polythiophene conjugates, emerged for their higher biocompatibility, ionic as well as electronic conduction, and optical properties in the visible range. Electrochemical doping/dedoping is key for modulating OMIEC’s conductivity, charge storage and volume, enabling high performing bioelectronic devices such as recording and stimulating electrodes, transistors-based sensors and actuators. Remarkable results have been obtained interfacing polythiophenes-based transistors and actuators with mammalian cells as well as plants. However, electrochemical doping has not been explored to the same extent for modulating the mechanical properties of OMIECs on demand and for drug delivery applications.

We first investigated the doping/de-doping behaviour of a representative glycolated polythiophene (p(g3T2)). According to previous publications, our findings show that the electrochemical doping involves volumetric change in aqueous environment. We report a qualitative and quantitative study on how the mechanical properties change in-situ during electrochemical doping and de-doping for p(g3T2). Its Young’s Modulus changes from 69 MPa in the dry state to less than 10 MPa in hydrated state and then further decreases down to 0.4 MPa when electrochemically doped, representing the largest modulation reported for an OMIEC so far. Additionally, we demonstrate that the amount of volumetric change, hence the viscoelastic changes, depend on the ionic strength of the solvent and on the polymer’s side chain design.

Then, we harnessed the volumetric exchange for controlled drug delivery. By reversibly expanding up to 300% during doping, p(g3T2) forms pores in the nm-size range resulting in a conducting hydrogel. P(g3T2)-coated 3D carbon sponges enable temporally patterned loading and release of molecules, spanning molecular weights of 800-6000 Da, from simple dyes up to the hormone insulin. Molecules are loaded as a combination of electrostatic interactions with the charged polymer backbone and physical entrapment in the porous matrix.

Overall, our findings deterministically correlate the mechanical properties, the volume changes and the doping state of the material, laying the basis for the development of electrically addressable devices. This class of material and devices has a great potential interest for bioelectronics’ applications, as it accounts for ionic/electronic conduction and on-demand modification of stiffness, emerging as a smart platform for mammalian and plant cell stimulation and monitoring.

Low-intensity focused ultrasound (LIFU) was discovered to have an excitatory effect in neuronal circuits approximately 15 years ago. Ever since that seminal work was published [1], hundreds of researchers worldwide have continuously investigated LIFU for brain stimulation, both for neuroscience and clinical translation. The reason for the excitement around LIFU is apparent: the low absorption and scattering together with the millimetric wavelengths of ultrasound in soft tissues, such as the brain, means that ultrasound can be transmitted from a distance, such as from the surface of the skull or brain, and be accurately focused with a neuromodulatory dosage in a millimetric spot anywhere in the brain, without affecting nor damaging the neurons in the propagation path [2]. Consequently, LIFU can be a happy medium between the precision of electrical deep brain stimulation and the non-invasiveness of transcranial magnetic stimulation while potentially having a considerably higher benefit-risk ratio [3]. The fact that there are currently ~100 clinical trials exploring LIFU for diseases such as Parkinson’s, Alzheimer’s, and Treatment Resistant Depression further showcases the great potential of this neuromodulation technology.

In the past 15 years, however, focused ultrasound transducer technology has not accompanied the fast developments of LIFU discoveries. These transducers, which generate focused ultrasound waves, still have a handheld/helmet bulky-form factor and require benchtop electronics [2]. Consequently, they are not compatible with the scales of rodents for pre-clinical research, are prohibitively large, and are power inefficient for use as a wearable LIFU neurostimulator.

Similar to the developments we saw in electrical stimulation, where large electrodes and bulky implantable pulse generators (IPGs) are being miniaturized into chip form factors, the field of ultrasound transducer technology is demanding the same revolution. In this talk, I will describe my group’s efforts towards this goal by focusing on novel ultrasound transducer microfabrication and microsystem integration methods and next-generation ultrasound electronics for two specific cases: full monolithic integration of ultrasound transducers on top of the integrated electronic chips for maximum level of miniaturization towards freely-moving experiments in rodents [4-6]; integration of ultrasound transducers and electronic chips in flexible substrates for large-aperture conformable ultrasonic neurostimulators, for deep brain stimulation in humans.

Current solutions for hearing impairment lie vastly in cochlear implants (CIs). However, they are limited by bulky, power-demanding external discomfortable components that hinder sound localization and suboptimal neural interfaces which negatively impact the efficiency of hearing restoration. To overcome these issues, I aim to exploit novel internal ion-gated electrochemical transistors (IGTs) and piezoelectric (PVDF) nanofibers to establish a soft, biocompatible artificial basilar membrane (ABM) for a fully implantable and self-contained CI. We hypothesize that organic electronics can create all the required components; IGT-based acousto-electrical transducers with a high signal-to-noise ratio (SNR), and low-impedance, stable stimulation electrodes. This will lead to a membrane with 8 intracochlear excitation points that conforms to the intact basilar membrane, generates, and amplifies electrical pulses (&gt;x10³) according to incoming acoustic stimuli, to stimulate the spiral ganglion neurons and restore hearing without external components. To achieve that, we create efficient and fast acousto-sensitive IGTs (gm/&tau; &gt; 10⁶ mSs^-1), high capacitance conductive polymer films, overcome stability issues and design smart fabrication routes that allow the development of all components into a single conformable substrate. We achieve that by tuning materials composition, improving designs, and better understanding the geometry and morphology effects on piezoelectric nanofibers. We explore IGT-arrays gated by continuous electrospun PVDF nanofiber (~0.6&micro;m fiber dia) films with gradually decreasing areas, to provide a deeper understanding of the device physics and elucidate their exact operating principle under various acoustic stimulations (0.1-10kHz). We also investigate the effect of the of acousto-sensitive IGT arrays on cell viability (&gt;70%)&nbsp; and their electrical interface with tissue (8kΩ @ 1kHz) in-vitro. We examine their performance in-vivo by recording the electrically evoked auditory brain recordings (ABRs)&nbsp; in a rat model.</p> <p>&nbsp;</p> <p>This project will generate safer, smaller, and more conformable acoustic-sensitive devices and stimulation electrodes that will build an ABM that can modulate the electrically neurophysiological activity of the spiral ganglion neurons. Further, the materials and methods that will be used in this project will lay the foundation for cost-effective and improved neurological devices such as micro-EEG systems and brain stem implants

Introduction
Electrochemical impedance spectroscopy (EIS) is commonly employed in the measurement of time-evolving biological tissue state[1]. As a small-signal linearization of the net electrochemical system, the measured impedance is a superposition of both the biological system under test as well as the current-voltage transfer characteristics of the counter and working electrodes. Consequently, a limitation of the two electrode (2E) configuration is the occlusion of the impedance of the biological system by the addition of the impedances of the electrodes. A common remedy is to employ a reference electrode (RE) in a three electrode (3E) configuration, effectively excluding the impedance contribution of the counter electrode[2]. However, in many cases, the 3E configuration is not considered practicable, as true REs are costly and challenging to integrate at scale into in vitro systems and in vivo implantations; while pseudo-reference electrodes (pREs) are considered inappropriate, due to their current-dependent interfacial potential, which introduces measurement uncertainty. We propose that for small-signal measurements of biological systems, pREs may, in fact, be utilized to improve measurement sensitivity, relative to the 2E configuration and present a framework for rationally designing pREs.

Results & Discussion
The two modes of error which arise from the use of pREs are distortion of the electric field applied to the biological system under test and instabilities in pRE potential which results in uncertainty in the measurement of the electrolyte potential (to which the working electrode potential is referred). Using finite element modelling we demonstrate an approach to the design of electrode geometry so as to minimize the distortion of the applied electric field, and consequently the distribution of ionic flux through the biological system. Using small-signal modelling of the net system, we derive an expression for the error introduced by fluctuations in pRE potential, which instructs the choice of material properties and key electrode geometries, and their impact on measurement certainty. A common use case of EIS for biological systems is the measurement of tissue barrier function, namely that of epithelial tissues, such as the intestinal mucosa and the skin[3]. Equivalent circuit fitting of the EIS spectra is utilized to extract metrics which are correlated to biological state, such as the paracellular resistance and transcellular capacitance. Through application of the proposed design framework, we construct a system for hosting and impedimetrically monitoring 3D cell cultures of barrier tissues, incorporating a stainless steel pRE. Using tissue phantoms, we extract relevant circuit parameters using the conventional 2E configuration and the pRE 3E configuration. Furthermore, we culture a 3D organotypic model of a commonly used epithelial tissue system and demonstrate a significant improvement in the accuracy of both the impedance spectra as well as the extracted paracellular resistance parameter, which is correlated to the well known transepithelial electrical resistance (TEER). 

Conclusion
We present a framework for rationally designing pREs such that the error introduced into the measurement is both quantified and mitigated.  We demonstrate that simple, cost effective, polarizable materials such as stainless steel can be used to improve the sensitivity of the measurement of tissue barrier function, which we validate using both tissue phantoms as well as an epithelial tissue model in a bioelectronic organ-on-chip platform.

Interacting with the human body using a range of modalities (i.e., electricity, light, ultrasound), holds great potential in increasing the resolution and specificity of neuromonitoring and neuromodulation. Neuroelectronic interfaces that are compatible with more than a single modality can serve as a valuable tool for neuroscientific research. This talk will describe recent research in the development of such multimodal neural interfaces. The first part of this talk will discuss the wafer-level fabrication and performance of optically transparent and MRI-compatible graphene-based in vivo and in vitro neural interfaces. Such interfaces enable concurrent optogenetic stimulation and electrophysiology, as well as two-photon imaging during electrical stimulation. The devices discussed here are fabricated using a unique transfer-free process which leads to a multi-layer graphene with the highest charge storage capacity among all reported CVD-graphene electrodes to date. During the second part, this talk will focus on the development of ultrasound-compatible neuroelectronics to enable systematic studies to elucidate the mechanisms of ultrasound neuromodulation. 

Biomaterial scaffolds enable 3D cultures of cells which better resemble biological systems, while advancements in bioelectronics have enabled the modulation of cells. Here, we describe various materials systems which enable soft material bioelectronics. First, we fabricate porous conductive hydrogels with the same mechanical modulus and viscoelasticity as neural tissue. The mechanical and electrical properties of the material can be tuned and used to modulate the growth and differentiation of various cell types. Application of exogenous electrical stimulation can then be applied to the scaffolds to further modulate cells. To investigate the functionality of neurite networks in 3D, we combine polydimethylsiloxane (PDMS) microstructures with multielectrode arrays. We then integrate hydrogels into the PDMS microstructures, such that the hydrogel can facilitate neurons to form 3D networks while still confined by the PDMS. Both biomaterial platforms can support the growth of neuronal cells for over 8 weeks, and can be integrated into multimaterial systems to better understand neuronal development and disease.

The microbiome- gut-brain axis (MGBA), has emerged as an incredibly important, but complex, part of human physiology. Dysregulation or disruption of the MGBA is implicated in a host of pathologies that affect brain and gut (e.g. Autism Spectrum disorder, Crohn’s disease) but also whole body disorders where inflammation and metabolism are affected. Physiologically relevant in vitro human models, as well as advanced tools to study in vivo animal models, are urgently required to elucidate mechanisms in MGBA. In this talk I’ll discuss a new generation of electronic tools, based on conducting polymers, for understanding the MGBA.  First, I’ll discuss our progress towards generating a complete platform of the human MGBA with integrated monitoring and sensing capabilities. We use tissue mimetic conducting polymer scaffolds to build human-based models of the gut and brain which can then be used to study different aspects of MGBA in health and disease. Second, I’ll discuss conformable electronic devices we’ve developed for both ex-situ measurements of GI tissue from rats, as well as in vivo experiments in live rats. These devices allow highly sensitive monitoring of gut permeability and motility, as well as the enteric nervous system.

Human neural spheroids, 3D cellular aggregates of neurons and glial cells, are a compelling biological model for studying neuronal communication in physiological and pathological conditions, such as neurodevelopment and traumatic brain injury (TBI), respectively. This study introduces a novel design for a free-standing, fully perforated, and stretchable microelectrode array (MEA) specifically tailored to monitor the electrophysiological activity of brain spheroids under varying static and dynamic mechanical loads.

Our MEAs are fabricated using thin-film technology and composed of a platinum layer sandwiched between two 1 μm thick polyimide films. The stretchability of the MEA is achieved through a Kirigami-based patterning technique, incorporating μm-sized Y-shaped motifs in the MEA that facilitate out-of-plane deflections in plastic/metal/plastic microstructures [1][2]. The thin and freestanding MEAs are clamped between customised holders suitable for electrochemical and mechanical evaluation.

Using finite element modelling, we demonstrated that the electrode geometry, the relative substrate-to-metal width ratio, and metal thickness collectively influenced the overall stretchability of the electrode, affecting the resulting maximum strain on the metallic layer upon elongation. Optimization of these parameters reduced the maximum strain on the metal by half.

Experimental validation involved applying uniaxial elongation at a constant speed (100 μm/s) to the MEA with strain parameters aligned with what is typically seen in TBI (5-30% strain). Scanning electron micrographs of the patterned electrodes upon stretching confirmed the results of the numerical simulations, identifying the electrode as the most fragile component of the MEA. Structural failure was observed at the electrode edge, occurring at 25% strain for the optimized electrodes. To verify the functionality of the electrodes while stretching, we monitored their electrochemical impedance at 1 kHz upon elongation. Optimized electrodes sustained strains up to 10% without a significant increase in their electrochemical impedance amplitude, while unoptimized electrodes sustained strains only up to 7.5% (n_MEAs = 3, n_electr = 24 per condition).

Additionally, we evaluated the impact of an electrodeposited Poly(3,4-ethylenedioxythiophene) (PEDOT) coating on the electrode stretchability. The PEDOT coating conformed to the patterned electrodes independently of the electrode size and reduced the electrochemical impedance at 1 kHz by 60 folds (n = 24, diameter = 70 μm). The PEDOT coating deformed together with the electrode during elongation. The PEDOT-coated electrodes exhibited more stable impedance under mechanical loading compared to bare platinum electrodes, therefore enhancing both their electrical and mechanical performance.

Finally, we verified the functionality of the stretchable electrodes in recording neural activity from brain spheroids. Each MEA hosted eight Kirigami-patterned recording electrodes (diameter = 70 μm), and a large ground electrode to probe one brain spheroid (spheroid diameter = 500-1000 μm). The MEAs reliably recorded spontaneous neural activity from brain spheroids for up to five days when mounted on a fluidic platform for cell culture media change.

This work paves the way for studying the effect of mechanical loading on neural activity in 3D in vitro brain models.

Regenerative medicine show huge therapeutic potential for neurodegenerative diseases and conditions of the nervous system (1). Challenging conditions such as central nervous system disorders (2), spinal cord injuries (3,4), and peripheral nerve malfunctions could potentially be treated by controlling neuron regeneration via stem cells, as recently has been proven in the clinic (5). At this stage, our understanding of stem cell development and neurogenic differentiation remains limited. There is an urgent need for advanced in vitro platforms for understanding these crucial stem cell properties to support further exploitation in the clinic. Here, we show the development of conducting hydrogels and their use as a 3D  in vitro bioelectronic platform to study the development of neural networks from human induced pluripotent stem cells (iPSCs). Taking advantage of the unique solution mixing properties of conducting polymers (6), we combined PEDOT:PSS (7) with extracellular matrix materials (ECM) to synthesize biocompatible, conductive and transparent hydrogels under physiological conditions. While the in vivo microenvironment for 3D neural networks is replicated, the gels were also mechanical compatible with neural tissue as well electrically active. The transmittance of the hydrogel is found to approximately 50% in the optical spectra range of 300-800 nm for thickness at 400 μm. Detailed electrochemical characterization via impedance spectroscopy and cyclic voltammetry  revealed that PEDOT:PSS intercalation within the hydrogel network gives rise to high charge storage capacitance and current. We believe the results presented here pave the way for hydrogel bioelectronics as 3D platforms to monitor, control, and guide stem-cell-to-neuron differentiation with electrical cues.

The skin is the largest organ in the human body and consists of several layers, the outermost of which is the epidermis. Keratinocytes, the predominant cell type in the epidermis, are essential for maintaining skin integrity and barrier function. During wound healing, the dynamic process of proliferation, differentiation and apoptosis of keratinocytes, which are typically involved in the continuous renewal of the epidermis, is accelerated [1].

These processes can be further modulated by nanostructured devices based on conjugated polymers and sensible to the green light to facilitate re-epithelialization of the wound site. Active interfaces with nanoscale components are particularly useful for interfacing and adapting to the complex nanoscale structural features of living tissues. Conjugated polymers are emerging as optimal candidates for interacting with living organisms due to their high biocompatibility and ability to combine the chemical and mechanical advantages of organic materials with the unique optoelectronic properties of semiconductors. Poly(3-hexylthiophene-2,5-diyl) (P3HT) is the chosen organic and photoelectrochemically active conjugated polymer. As a semiconductor, P3HT modulates the cell membrane potential through its interaction with cells, absorbing light in the visible spectrum and supporting charge photogeneration, which sustains both electronic and ionic charge transport [2].

In this work we report the synthesis and optoelectronic and morphological characterization of biocompatible and photosensitive platform capable of modulating the epithelial cells physiology. P3HT-based devices have the potential to open new frontiers in regenerative medicine, with significant implications for therapeutic strategies in the treatment of skin injuries and chronic wounds.

In this talk I will present our research activities using a vibrational probe to understand the effect of structure and interactions between molecules on the photophysical behavior of a conjugated polyelectrolyte. Resonance Raman spectroscopy can provide ground state information on the conformation of conjugated polymers under various environmental conditions, be it either temperature, solvent processing conditions, the film matrix, or under various chemical modifications. However, the intensity of the Raman bands in a resonant experiment contains rich information that has been underexplored in organic electronics. I will show how we employ the tools provided by this spectroscopic method to understand the sequence-dependent templating effect of single-stranded DNAs (ssDNAs) on the conformation of conjugated polyelectrolytes and consequently on the photophysical properties and excited state dynamics of a class of cationic polythiophenes (CPT) originally designed as a biosensor for detecting infection and genetic diseases. [1] Combining the selectivity provided by resonance Raman for a particular chromophore we were able to understand the interactions between a CPT and different ssDNAs that lead to particular templated conformations of the polymer. [2] Resonance Raman intensity analysis then provided insights on the excited state vibrational-mode-dependent reorganization as a function of the extent of interactions between the polymer and the ssDNA. Finally, we combined this information with ultrafast transient absorption experiments in the near- and mid-IR to understand the effect of structural templating on the excited state processes. [3] We found that while certain ssDNA sequences can induce order in the conjugated polymer backbone through extensive interactions between the two partners in the complex, the templating scaffold does not seem to be a mere spectator but instead participates and affects the excited state behaviour. This is something that needs to be considered in the design of functional templated conjugated polyelectrolytes for their suitability for particular bioelectronic applications.

Electrochemical transistors (OECTs) have been shown to be promising devices for amplification of electrical signals and selective sensing of ions and biologically important molecules in an aqueous environment, and thus have potential to be utilised in bioelectronic applications. The sensitivity, selectivity and intensity of the response of this device is determined by the organic semiconducting polymer employed as the active layer. This presentation will discuss the role of glycol and alkyl chains on optimizing the trade-off between ion uptake through hydrated channels, facilitated by hydrophilic chains, and self-assembly driven ordering within the semiconducting domains, facilitated by hydrophobic chains. We show the design of new organic semiconducting materials which demonstrate good OECT performance, through operation in accumulation mode, with high transconductance and low operating voltage.  Key aspects such as ion and charge transport in the bulk semiconductor and operational voltage and stability of the devices are addressed in order to elucidate important structure-property relationships. A range of new semiconducting polymers, designed to exhibit facile electrochemical doping of either holes or electrons, facilitate ion penetration and migration, as well as have aqueous compatibility are reported. Optimisation of a series of polymer parameters including electrochemical doping, charge carrier mobility and capacitance are discussed.

Immobilization of DNA on gold nanoparticles (GNPs) is an important consideration in electrochemical biosensing. Non-covalent immobilization of DNA on GNPs utilizes the intrinsic affinity of DNA bases to GNPs and provides a simple and convenient method of immobilization, thereby circumventing the time-consuming and costly techniques for DNA labelling or functionalized electrode preparation for DNA conjugation ^[1]. Researchers have reported the use of non-covalent adsorption of DNA on metallic electrode surfaces for electrochemical biosensing, but the mechanism of binding has not been much explored ^{[1, 2]}. In this study, we propose how different non-covalent DNA immobilization conditions alter the conformation of oligonucleotides on gold nanoparticles. We conduct a fundamental study for the adsorption of short model oligonucleotides onto gold nanoparticles (GNPs). It is observed that the variation in solution conditions has a profound effect on the way in which oligonucleotides bind to GNPs. We hypothesize the binding phenomena to be a contribution of several factors: base composition, strand directionality, competition of oligonucleotides to bind to GNPs or undergo inter-strand assembly, among others. In addition to these factors, the properties of the individual bases in the given solution conditions (such as protonation or deprotonation) also affect the way in which the oligonucleotide strand binds to GNPs. We foresee using this understanding to be helpful in the development of biosensors utilizing nucleotide conjugated nanoparticles as sensing elements. 

References:

[1] Yang, Y., Li, C., Yin, L., Liu, M., Wang, Z., Shu, Y., & Li, G. (2014). Enhanced charge transfer by gold nanoparticle at DNA modified electrode and its application to label-free DNA detection. ACS applied materials & interfaces, 6(10), 7579-7584.

[2] Zhang, Q., & Subramanian, V. (2007). DNA hybridization detection with organic thin film transistors: Toward fast and disposable DNA microarray chips. Biosensors and Bioelectronics, 22(12), 3182-3187.