Fully Printed μ-Needle Electrode Array from Conductive Polymer Ink for Bioelectronic Applications

Microelectrode arrays (MEAs) are widely used platforms in bioelectronics to study electrogenic cells. In recent years, the processing of conductive polymers for the fabrication of three-dimensional electrode arrays has gained increasing interest for the development of novel sensor designs. Here, additive manufacturing techniques are promising tools for the production of MEAs with three-dimensional electrodes. In this work, a facile additive manufacturing process for the fabrication of MEAs that feature needle-like electrode tips, so-called μ-needles, is presented. To this end, an aerosol-jet compatible PEDOT:PSS and multiwalled carbon nanotube composite ink with a conductivity of 323 ± 75 S m–1 is developed and used in a combined inkjet and aerosol-jet printing process to produce the μ-needle electrode features. The μ-needles are fabricated with a diameter of 10 ± 2 μm and a height of 33 ± 4 μm. They penetrate an inkjet-printed dielectric layer to a height of 12 ± 3 μm. After successful printing, the electrochemical properties of the devices are assessed via cyclic voltammetry and impedance spectroscopy. The μ-needles show a capacitance of 242 ± 70 nF at a scan rate of 5 mV s–1 and an impedance of 128 ± 22 kΩ at 1 kHz frequency. The stability of the μ-needle MEAs in aqueous electrolyte is demonstrated and the devices are used to record extracellular signals from cardiomyocyte-like HL-1 cells. This proof-of-principle experiment shows the μ-needle MEAs’ cell-culture compatibility and functional integrity to investigate electrophysiological signals from living cells

Inkjet-Printed and Electroplated 3D Electrodes for Recording Extracellular Signals in Cell Culture

Recent investigations into cardiac or nervous tissues call for systems that are able to electrically record in 3D as opposed to 2D. Typically, challenging microfabrication steps are required to produce 3D microelectrode arrays capable of recording at the desired position within the tissue of interest. As an alternative, additive manufacturing is becoming a versatile platform for rapidly prototyping novel sensors with flexible geometric design. In this work, 3D MEAs for cell-culture applications were fabricated using a piezoelectric inkjet printer. The aspect ratio and height of the printed 3D electrodes were user-defined by adjusting the number of deposited droplets of silver nanoparticle ink along with a continuous printing method and an appropriate drop-to-drop delay. The Ag 3D MEAs were later electroplated with Au and Pt in order to reduce leakage of potentially cytotoxic silver ions into the cellular medium. The functionality of the array was confirmed using impedance spectroscopy, cyclic voltammetry, and recordings of extracellular potentials from cardiomyocyte-like HL-1 cel

Biocompatible, Flexible, and Oxygen-Permeable Silicone-Hydrogel Material for Stereolithographic Printing of Microfluidic Lab-On-A-Chip and Cell-Culture Devices

We present a photocurable, biocompatible, and flexible silicone-hydrogel hybrid material for stereolithographic (SLA) printing of biomedical devices. The silicone-hydrogel polymer is similar to mixtures used for contact lenses. It is flexible and stretchable with a Young’s modulus of 78 MPa and a maximum elongation at break of 51%, shows a low degree of swelling (<4% v/v) in water, and can be bonded easily to flat glass substrates via a surface-modification method. The in vitro cytotoxicity of the material is assessed with a WST-8 cell viability assay using five different cell lines: HT1080, L929, and Hs27 fibroblasts, cardiomyocyte-like HL-1 cells, and neuronal-phenotype PC-12 cells. On this account, the silicone-hydrogel polymer is compared to several other common SLA printing materials used for cell-culture applications and polydimethylsiloxane (PDMS). A simple extraction step in water is sufficient for reaching biocompatibility of the material with respect to the tested cell types. The oxygen permeability of the silicone-hydrogel material is investigated and compared to that of PDMS, Medicalprint clear—a commercial resin for medical products, and a short-chain hydrogel-based resin. As a proof of concept, we demonstrate a 3D-printed microfluidic device with integrated valves and mixers. Furthermore, we show a printed culture chamber for analyzing signal propagation in HL-1 cardiomyocyte cell networks. Ca2+ imaging is used to observe the signal propagation through the cardiac cell layers grown in the microchannels. The cells are shown to maintain normal electrophysiological activity within the printed chambers. Overall, the biocompatible silicone-hydrogel material will be an advancement for SLA printing in cell-culture and microfluidic lab-on-a-chip applications

Repurposing Disulfiram for Targeting of Glioblastoma Stem Cells: An In Vitro Study

Mesenchymal glioblastoma stem cells (GSCs), a subpopulation in glioblastoma that are responsible for therapy resistance and tumor spreading in the brain, reportedly upregulate aldehyde dehydrogenase isoform-1A3 (ALDH1A3) which can be inhibited by disulfiram (DSF), an FDA-approved drug formerly prescribed in alcohol use disorder. Reportedly, DSF in combination with Cu2+ ions exerts multiple tumoricidal, chemo- and radio-therapy-sensitizing effects in several tumor entities. The present study aimed to quantify these DSF effects in glioblastoma stem cells in vitro, regarding dependence on ALDH1A3 expression. To this end, two patient-derived GSC cultures with differing ALDH1A3 expression were pretreated (in the presence of CuSO4, 100 nM) with DSF (0 or 100 nM) and the DNA-alkylating agent temozolomide (0 or 30 µM) and then cells were irradiated with a single dose of 0–8 Gy. As read-outs, cell cycle distribution and clonogenic survival were determined by flow cytometry and limited dilution assay, respectively. As a result, DSF modulated cell cycle distribution in both GSC cultures and dramatically decreased clonogenic survival independently of ALDH1A3 expression. This effect was additive to the impairment of clonogenic survival by radiation, but not associated with radiosensitization. Of note, cotreatment with temozolomide blunted the DSF inhibition of clonogenic survival. In conclusion, DSF targets GSCs independent of ALDH1A3 expression, suggesting a therapeutic efficacy also in glioblastomas with low mesenchymal GSC populations. As temozolomide somehow antagonized the DSF effects, strategies for future combination of DSF with the adjuvant standard therapy (fractionated radiotherapy and concomitant temozolomide chemotherapy followed by temozolomide maintenance therapy) are not supported by the present study

Aerosol Jet-Printed High-Aspect Ratio Micro-Needle Electrode Arrays Applied for Human Cerebral Organoids and 3D Neurospheroid Networks

The human brain is a complex and poorly accessible organ. Thus, new tools are required for studying the neural function in a controllable environment that preserves multicellular interaction and neuronal wiring. In particular, high-throughput methods that alleviate the need for animal experiments are essential for future studies. Recent developments of induced pluripotent stem cell technologies have enabled in vitro modeling of the human brain by creating three-dimensional brain tissue mimic structures. To leverage these new technologies, a systematic and versatile approach for evaluating neuronal activity at larger tissue depths within the regime of tens to hundreds of micrometers is required. Here, we present an aerosol-jet- and inkjet-printing-based method to fabricate microelectrode arrays, equipped with high-aspect ratio μ-needle electrodes that penetrate 3D neural network assemblies. The arrays have been successfully applied for electrophysiological recordings on interconnected neurospheroids formed on an engineered substrate and on cerebral organoids, both derived from human induced pluripotent stem cells

Inna Jamaican Stylee

Volume ! propose dans ce numéro un dossier consacré à l’étude des musiques jamaïcaines. Les neuf textes qui le composent, accompagnés de douze recensions d’ouvrages majeurs et récents, offrent une description et une analyse des principaux traits caractéristiques de ces musiques, à travers leurs usages – des riddims aux sound systems – et leurs discours – de la culture au slackness. Cet état des lieux du champ réunit les plus grands spécialistes et nous plonge dans les principaux débats associés à ces musiques. This special issue of Volume! is dedicated to Jamaican music. Its nine texts, along with a dozen reviews of major recent books, offer a description and an analysis of the main features of these musics, through their uses – from riddims to sound sytems – and discourses – from culture to slackness. Gathering works from leading scholars in the field, this survey sheds new light on the main debates that stem from Jamaican popular music