We report a lung-on-a-chip array that mimics the pulmonary parenchymal environment, including the thin alveolar barrier and the three-dimensional cyclic strain induced by breathing movements. The micro-diaphragm used to stretch the alveolar barrier is inspired by the in vivo diaphragm, the main muscle responsible for inspiration. The design of this device aims not only at best reproducing the in vivo conditions found in the lung parenchyma but also at making the device robust and its handling easy. An innovative concept, based on the reversible bonding of the device, is presented that enables accurate control of the concentration of cells cultured on the membrane by easily accessing both sides of the membranes. The functionality of the alveolar barrier could be restored by co-culturing epithelial and endothelial cells that form tight monolayers on each side of a thin, porous and stretchable membrane. We showed that cyclic stretch significantly affects the permeability properties of epithelial cell layers. Furthermore, we also demonstrated that the strain influences the metabolic activity and the cytokine secretion of primary human pulmonary alveolar epithelial cells obtained from patients. These results demonstrate the potential of this device and confirm the importance of the mechanical strain induced by breathing in pulmonary research.

The presence of heavy metal ions such as copper in the human body at certain concentrations and specific conditions can lead to the development of different diseases. The currently available analytical detection methods remain expensive, time-consuming, and often require sample pre-treatment. The development of specific and quantitative, easy-in-operation, and cost-effective devices, capable of monitoring the level of Cu²⁺ ions in environmental and physiological media, is necessary. We use silicon nanoribbon (SiNR) ion-sensitive field effect transistor (ISFET) devices modified with a Gly–Gly–His peptide for the detection of copper ions in a large concentration range. The specific binding of copper ions causes a conformational change of the ligand, and a deprotonation of secondary amine groups. By performing differential measurements, we gain a deeper insight into the details of the ion–ligand interaction. We highlight in particular the importance of considering non-specific interactions to explain the sensors’ response.

In automation, transportation, and consumer applications, countless products rely on low-cost, accurate angle sensors. A common method to realize such an angle sensor in CMOS technology utilizes two Vertical Hall Devices (VHDs) to measure the direction of the in-plane magnetic field components of a rotating permanent magnet through corresponding sine and cosine signals. However, the accuracy of VHD based angle sensors was found to be compromised by, e.g., misalignment and imperfections of the fabrication processes and mechanical stress due to the piezo-Hall effect leading to non-orthogonality due to crosstalk between sine and cosine signals originating from stress-related changes of the sensitive directions. In this work we present an active compensation method for the shear stress related directional sensitivity of VHD based angle sensors. The method translates the signal of a cointegrated piezoresistive shear stress sensor into cross-talk compensation counterbalancing the direction changes and therefore re-establishing orthogonality between sine and cosine signals. The method was demonstrated with CMOS-integrated VHD and stress sensors exposed to in-plane shear stress in a torsional bridge setup at temperatures between 26°C and 96°C. As a result, at 26°C and 21 MPa stress, the standard deviation of the measured orthogonality error decreased from 2.5° to a noise-limited 0.28°, while the systematic orthogonality error was significantly reduced from 3.6° to 0.1° after compensation. This significant improvement underscores the effectiveness of the active compensation method in mitigating the impact of mechanical stress, thereby enhancing the accuracy and reliability of VHD-based angle sensors.

The effect of the mechanical stretch associated with breathing on lung pneumocytes is of great importance in regulating lung functions. Standard in-vitro lung alveolar models do not mimic this dynamic environment. In addition, most of those models use a cancer cell line that further counteracts the human lung in-vivo situation. We recently developed a lung-on-a-chip able to mimic the mechanical stress of the thin alveolar barrier. The goal of this study is to characterize the effects of mechanical stretch on primary human alveolar epithelial cells obtained from five patients. Primary human pulmonary alveolar epithelial cells from patients undergoing lung resections were sorted by FACS and cultured in the lung-on-a-chip, as described previously (Stucki, AO et al. Lab Chip 2015). Cells from a total of 5 patients were grown to confluence for 48h. The cells were then exposed to 3D cyclic, physiological, mechanical stretch (10% linear, 0.2Hz) during 48h. The supernatant was collected daily for analysis of secreted factors such as IL-8 or IL-6. After 48h, RNA was harvested for gene expression analysis. Results showed a significantly increased release of IL-8 after 48h of stretch compared to a static control (9.7±2.6 ng/ml vs. 3.8±1.6 ng/ml, n=3). These findings are in accordance to results obtained in cell lines. We could show that mechanical stretch has an effect on primary human pulmonary alveolar epithelial cells, which may be of importance in regulating lung functions. Genetic analysis and expression profiles of cytokines and cytokine-related genes performed on those cells are currently on-going. Those results are expected to provide a more complete picture of the effect of mechanical stretch on patients9 cells.