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.

Electrochemical paper-based analytical devices (ePADs) offer an innovative, low-cost, and environmentally friendly approach for real-time diagnostics. In this study, we developed a functional all-inkjet paper-based electrochemical immunosensor using gold (Au) printed ink to detect salivary cortisol. Covalent binding of the cortisol monoclonal antibody onto the printed Au surface was achieved through electrodeposition of 4-carboxymethylaniline (CMA), with ethanolamine passivation to prevent non-specific binding. The ePAD exhibited a linear response within the physiological cortisol range (5–20 ng/mL), with sensitivities of 25, 23, and 19 Ω·ng/mL and R² values of 0.995, 0.979, and 0.99, respectively. Additionally, interference studies against tumor necrosis factor-α (TNF-α) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) yielded excellent results. This novel ePAD, fabricated using inkjet printing technology on paper, simplifies the process, reduces environmental impact, and lowers fabrication costs.

There are a broad range of applications such as analytical sensors, biosensing and medical applications that require the monitoring of dissolved oxygen (DO) and pH using sensitive, stable, compact and low cost sensors. Here we develop full inkjet printing sensors to measure DO and pH. They have been fabricated using commercially available gold and platinum inks in plastic substrates. The inks are specially designed formulation which allows their sintering at temperatures as low as 150 and 190 °C for Au and Pt respectively. This is a key point in the development of low-cost sensors made on plastic and paper substrates. These sensors integrate in a single platform all the basic elements for pH and DO recording, allowing the measures without any external electrode. The DO is directly measured with a gold working electrode, and the pH sensors is achieved after electrodepositing iridium oxide film over platinum working electrode. The printed electrodes for DO sensing exhibits excellent linearity between 0 and 8 mg L ^{_ 1} range, with correlation factors greater than 0.99, obtaining low limits of detection, 0.17 mgL ^{_ 1} and a sensitivity of 0.06 A(mgL) ^{_ 1}. IrOx pH sensors exhibit a super-Nernstian response in sensitivity repeatedly and reversibly between 65 mV/pH in the pH range of 3 to 10. This work demonstrates that these sensors are suitable for the determination of DO and pH and provide a cost-effective solution for future electrochemical monitoring systems.