Hydrophobic Eutectogels as Electrodes for Underwater Electromyography Recording.

Underwater recording remains a critical challenge in bioelectronics because traditional flexible electrodes can not fulfill essential requirements such as stability and steady conductivity in aquatic environments. Herein, we show the use of elastic gels made of hydrophobic natural eutectic solvents as water-resistant electrodes. These eutectogels are designed with tailorable mechanical properties via one-step photopolymerization of acrylic monomers in different eutectic mixtures composed of fatty acids and menthol. The low viscosity of the eutectics turns the formulations into suitable inks for 3D printing, allowing fast manufacturing of complex objects. Furthermore, the hydrophobic nature of the building blocks endows the eutectogels with excellent stability and low water uptake. The obtained flexible eutectogel electrodes can record real-time electromyography (EMG) signals with low interference in the air and underwater.

Digital Light 3D Printing of PEDOT-Based Photopolymerizable Inks for Biosensing.

3D conductive materials such as polymers and hydrogels that interface between biology and electronics are actively being researched for the fabrication of bioelectronic devices. In this work, short-time (5 s) photopolymerizable conductive inks based on poly(3,4-ethylenedioxythiophene) (PEDOT):polystyrene sulfonate (PSS) dispersed in an aqueous matrix formed by a vinyl resin, poly(ethylene glycol) diacrylate (PEGDA) with different molecular weights (M n = 250, 575, and 700 Da), ethylene glycol (EG), and a photoinitiator have been optimized. These inks can be processed by Digital Light 3D Printing (DLP) leading to flexible and shape-defined conductive hydrogels and dry conductive PEDOTs, whose printability resolution increases with PEGDA molecular weight. Besides, the printed conductive PEDOT-based hydrogels are able to swell in water, exhibiting soft mechanical properties (Young's modulus of ∼3 MPa) similar to those of skin tissues and good conductivity values (10-2 S cm-1) for biosensing. Finally, the printed conductive hydrogels were tested as bioelectrodes for human electrocardiography (ECG) and electromyography (EMG) recordings, showing a long-term activity, up to 2 weeks, and enhanced detection signals compared to commercial Ag/AgCl medical electrodes for health monitoring.

Flexible Organic Electronic Devices for Pulsed Electric Field Therapy of Glioblastoma.

Glioblastoma is difficult to eradicate with standard oncology therapies due to its high degree of invasiveness. Bioelectric treatments based on pulsed electric fields (PEFs) are promising for the improvement of treatment efficiency. However, they rely on rigid electrodes that cause acute and chronic damage, especially in soft tissues such as the brain. In this work, flexible electronics were used to deliver PEFs to tumors and the biological response was evaluated with fluorescent microscopy. Interdigitated gold electrodes on a thin, transparent parylene-C substrate were coated with the conducting polymer PEDOT:PSS, resulting in a conformable and biocompatible device. The effects of PEFs on tumors and their microenvironment were examined using various biological models. First, monolayers of glioblastoma cells were cultured on top of the electrodes to investigate phenomena in vitro. As an intermediate step, an in ovo model was developed where engineered tumor spheroids were grafted in the embryonic membrane of a quail. Due to the absence of an immune system, this led to highly vascularized tumors. At this early stage of development, embryos have no immune system, and tumors are not recognized as foreign bodies. Thus, they can develop fast while developing their own vessels from the existing embryo vascular system, which represents a valuable 3D cancer model. Finally, flexible electrode delivery of PEFs was evaluated in a complete organism with a functional immune system, using a syngenic, orthograft (intracranial) mouse model. Tumor spheroids were grafted into the brain of transgenic multi-fluorescent mice prior to the implantation of flexible organic electrode devices. A sealed cranial window enabled multiphoton imaging of the tumor and its microenvironment during treatment with PEFs over a period of several weeks.

Gelatin and Tannic Acid Based Iongels for Muscle Activity Recording and Stimulation Electrodes.

Iongels are soft ionic conducting materials, usually composed of polymer networks swollen with ionic liquids (ILs), which are being investigated for applications ranging from energy to bioelectronics. The employment of iongels in bioelectronic devices such as bioelectrodes or body sensors has been limited by the lack of biocompatibility of the ILs and/or polymer matrices. In this work, we present iongels prepared from solely biocompatible materials: (i) a biobased polymer network containing tannic acid as a cross-linker in a gelatin matrix and (ii) three different biocompatible cholinium carboxylate ionic liquids. The resulting iongels are flexible and elastic with Young's modulus between 11.3 and 28.9 kPa. The morphology of the iongels is based on a dual polymer network system formed by both chemical bonding due to the reaction of the gelatin's amines with the polyphenol units and physical interactions between the tannic acid and the gelatin. These biocompatible iongels presented high ionic conductivity values, from 0.003 and up to 0.015 S·cm-1 at room temperature. Furthermore, they showed excellent performance as a conducting gel in electrodes for electromyography and electrocardiogram recording as well as muscle stimulation.

PVDF-TrFE-Based Stretchable Contact and Non-Contact Temperature Sensor for E-Skin Application.

Development of stretchable electronics has been driven by key applications such as electronics skin for robotic or prosthetic. Mimicking skin functionalities imposes at a minimal level: stretchability, pressure, and temperature sensing capabilities. While the research on pressure sensors for artificial skin is extensive, stretchable temperature sensors remain less explored. In this work, a stretchable temperature and infrared sensor has been developed on a polydimethylsiloxane substrate. The sensor is based on poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) as a pyroelectric material. This material is sandwiched between two electrodes. The first one consists of aluminium serpentines, covered by gold in order to get electrical contact and maximum stretchability. The second one is based on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) that has shown good electrical compatibility with PVDF-TrFE and provides the stretchability of the top electrode. Without poling the PVDF-TrFE, sensor has shown a sensitivity of around 7 pF.°C-1 up to 35% strain without any change in its behaviour. Then, taking advantage on infrared absorption of PEDOT:PSS, a poled device has shown a pyroelectric peak of 13 mV to an infrared illumination of 5 mW at 830 nm. This stretchable device valuably allows an electronic skin (e-skin) use for contact and more importantly non-contact thermal sensing.

Effect of E Cigarette Emissions on Tracheal Cells Monitored at the Air-Liquid Interface Using an Organic Electrochemical Transistor.

E-cigarettes have been suggested as a potentially healthier alternative to cigarettes based on studies using cell viability, DNA damage, and transcriptional response assays. However, little is known about the effect of e-cigarette aerosols on the integrity of the tracheal epithelium, specifically with respect to barrier resistance. This is partly due to the lack of methods for monitoring epithelia at the air-liquid interface (ALI), i.e., under physiological conditions. Here, it is shown that an organic electrochemical transistor can be adapted for the measurement of barrier resistance at the ALI. This technology enables accurate, continuous quantification of tracheal barrier integrity through the use of a conformable gate electrode placed on top of the cell-secreted mucus, obviating the need for addition of culture medium or buffer as a conductance medium for rigid electrodes. This platform allows for the detection of a dose-dependent, rapid decrease in barrier resistance of an in vitro model of human bronchial epithelium (MucilAir) after E-cigarette aerosols exposure. The system represents a powerful tool to study tissue responses of the human airway epithelium to inhaled smoke. The same technology will have broad applications for toxicology studies on other tissues with ALI, including other airway tissues and skin.

Laser-patterned metallic interconnections for all stretchable organic electrochemical transistors.

We describe a process allowing the patterning of fully stretchable organic electrochemical transistors (OECTs). The device consists of an active stretchable area connected with stretchable metallic interconnections. The current literature does not provide a complete, simple and accurate process using the standard thin film microelectronic techniques allowing the creation of such sensors. An innovative patterning process based on the combination of laser ablation and thermal release tape ensures the fabrication of highly stretchable metallic lines - encapsulated in polydimethylsiloxane - from conventional aluminium tape. State-of-the-art stretchability up to 70% combined with ultra-low mOhms resistance is demonstrated. We present a photolithographic process to pattern the organic active area onto stretchable substrate. Finally the formulation of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) is tuned to achieve an OECT with a maximum stretchability of 38% while maintaining transconductance up to 0.35 mS and channel current as high as 0.2 mA.

Saccharomyces boulardii CNCM I-745 Restores intestinal Barrier Integrity by Regulation of E-cadherin Recycling.

BACKGROUND AND AIMS: Alteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease [IBD]. Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 [Sb], used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD. METHODS: We analyzed the impact of Sb supernatant on tissue integrity and components of adherens junctions using cultured explants of colon from both IBD and healthy patients. To evaluate the pathways by which Sb regulates the expression of E-cadherin at the cell surface, we developed in vitro assays using human colonic cell lines, including cell aggregation, a calcium switch assay, real-time measurement of transepithelial electrical resistance [TEER] and pulse-chase experiments. RESULTS: We showed that Sb supernatant treatment of colonic explants protects the epithelial morphology and maintains E-cadherin expression at the cell surface. In vitro experiments revealed that Sb supernatant enhances E-cadherin delivery to the cell surface by re-routing endocytosed E-cadherin back to the plasma membrane. This process, involving Rab11A-dependent recycling endosome, leads to restoration of enterocyte adherens junctions, in addition to the overall restoration and strengthening of intestinal barrier function. CONCLUSION: These findings open new possibilities of discovering novel options for prevention and therapy of diseases that affect intestinal permeability.

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring.

Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are two-fold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.