The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of organ-on-a-chip (OOC) systems. However, the incorporation of co-cultures and microfluidic channels in OOC systems increases their biological complexity and therefore makes the analysis and monitoring of analytical parameters inside the device more difficult. In this work, we present an approach to integrate multiple sensors in an extremely thin, porous and delicate membrane inside a liver-on-a-chip device. Specifically, three electrochemical dissolved oxygen (DO) sensors were inkjet-printed along the microfluidic channel allowing local online monitoring of oxygen concentrations. This approach demonstrates the existence of an oxygen gradient up to 17.5% for rat hepatocytes and 32.5% for human hepatocytes along the bottom channel. Such gradients are considered crucial for the appearance of zonation of the liver. Inkjet printing (IJP) was the selected technology as it allows drop on demand material deposition compatible with delicate substrates, as used in this study, which cannot withstand temperatures higher than 130 °C. For the deposition of uniform gold and silver conductive inks on the porous membrane, a primer layer using SU-8 dielectric material was used to seal the porosity of the membrane at defined areas, with the aim of building a uniform sensor device. As a proof-of-concept, experiments with cell cultures of primary human and rat hepatocytes were performed, and oxygen consumption rate was stimulated with carbonyl-cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), accelerating the basal respiration of 0.23 ± 0.07 nmol s-1/106 cells up to 5.95 ± 0.67 nmol s-1/106 cells s for rat cells and the basal respiration of 0.17 ± 0.10 nmol s-1/106 cells by up to 10.62 ± 1.15 nmol s-1/106 cells for human cells, with higher oxygen consumption of the cells seeded at the outflow zone. These results demonstrate that the approach of printing sensors inside an OOC has tremendous potential because IJP is a feasible technique for the integration of different sensors for evaluating metabolic activity of cells, and overcomes one of the major challenges still remaining on how to tap the full potential of OOC systems.
Sensor arrays used to detect electrophysiological signals from the brain are paramount in neuroscience. However, the number of sensors that can be interfaced with macroscopic data acquisition systems currently limits their bandwidth. This bottleneck originates in the fact that, typically, sensors are addressed individually, requiring a connection for each of them. Herein, we present the concept of frequency-division multiplexing (FDM) of neural signals by graphene sensors. We demonstrate the high performance of graphene transistors as mixers to perform amplitude modulation (AM) of neural signals in situ, which is used to transmit multiple signals through a shared metal line. This technology eliminates the need for switches, remarkably simplifying the technical complexity of state-of-the-art multiplexed neural probes. Besides, the scalability of FDM graphene neural probes has been thoroughly evaluated and their sensitivity demonstrated in vivo. Using this technology, we envision a new generation of high-count conformal neural probes for high bandwidth brain machine interfaces.
Recent advances in materials and manufacturing processes pave the way for the establishment of piezoelectric materials via printing techniques as flexible sensors, actuators, and generators. Such flexible devices are key building blocks for future advanced robotic skin and conformable medical devices. Herein special focus is given to printed devices for its lightweight, flexibility, and manufacturing by high throughput techniques, offering a disruptive advantage in integration technologies and a wide range of opportunities for industrialization routes, where cost‐effective applications are required. In this Progress Report, the different system parameters are discussed, pinpointing the ones that affect the production of reliable flexible printed piezoelectric devices and limit this technology to achieve higher technological maturity. Focus is made on screen and inkjet printing as fabrication techniques and the well‐established piezoelectric polymer poly(vinylidene fluoride‐co‐trifluoroethylene). Key limiting factors found for the manufacturing of robust scalable all‐printed piezoelectric devices stems mainly from the piezoelectric ink production and processing. Finally, the integration of these materials, via printing technologies, into soft, flexible, and even stretchable substrates is analyzed and insights are gathered on the manufacturing trends to achieve low‐cost production of flexible piezoelectric devices embedded in electronic skin and smart wearables.
Today, electrochemical sensors are used for a broad range of applications. A fundamental challenge is still the achievement of long-term sensor stability by ensuring good adhesion between the deposited sensing layer and the substrate material, e.g., a metal electrode. Until now, the most applied strategy to overcome this problem is to increase the surface roughness of the metal layer by mechanical etching or by electroplating of additional material layers, which both imply an increase in manufacturing steps and thus the final cost of the overall device. Alternatively, to overcome these adhesion problems, we propose the direct printing of a novel platinum nanoparticle ink, which is compatible with low-cost additive digital inkjet and with flexible low-cost substrates. This water-based platinum ink has two unique features: it leads to highly rough surfaces, which promotes the adhesion of deposited sensing material, and it is a highly low-temperature curing ink, compatible with polymeric substrates that cannot withstand high temperatures. Based on this concept, we report about a long-term stable and highly sensitive solid-state pH sensor functionalized by anodic electrodeposited iridium oxide on a rough nanostructured platinum printed layer. The sensors showed an excellent reproducibility with a linear super-Nernstian response (71.3 ± 0.3 mV/pH unit) in a wide pH range (pH 2–11). Long-term stability tests for over 1 year of application demonstrate an excellent mechanical sensor layer stability, which is correlated to the distinct roughness of the printed platinum layer. This novel approach is useful to simplify the fabrication process and with that the sensor costs.
With a growing demand for the availability of inexpensive, simple, and rapid prototyped devices, the prospect of miniaturization of the reference electrodes using printing techniques becomes promising. A stable and reusable full-inkjet-printed solid-state reference electrode (IPRE) was developed. The reference electrode was fully produced by consecutive inkjet printing of several layers. Ag ink was printed and chlorinated by NaClO printing, forming a Ag/AgCl pseudoreference electrode. Then a surface protection by printing a Cl–-saturated polyvinyl butyral membrane finally gave a reference electrode that demonstrated an outstanding performance comparable to commercial ones. This full inkjet printing fabrication strategy will improve the viability of producing low-cost miniaturized reference electrodes with interest in many electrochemical sensor-dependent areas.
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