NK cells eliminate virus-infected and tumor cells by releasing cytotoxic granules containing granzyme B (GrzB) or by engaging death receptors that initiate caspase cascades. The orchestrated interplay between both cell death pathways remains poorly defined. Here we simultaneously measure the activities of GrzB and caspase-8 in tumor cells upon contact with human NK cells. We observed that NK cells switch from inducing a fast GrzB-mediated cell death in their first killing events to a slow death receptor–mediated killing during subsequent tumor cell encounters. Target cell contact reduced intracellular GrzB and perforin and increased surface-CD95L in NK cells over time, showing how the switch in cytotoxicity pathways is controlled. Without perforin, NK cells were unable to perform GrzB-mediated serial killing and only killed once via death receptors. In contrast, the absence of CD95 on tumor targets did not impair GrzB-mediated serial killing. This demonstrates that GrzB and death receptor–mediated cytotoxicity are differentially regulated during NK cell serial killing.

In this article, we present OSTE+RIM, a novel reaction injection molding (RIM) process that combines the merits of off-stoichiometric thiol–ene epoxy (OSTE+) thermosetting polymers with the fabrication of high quality microstructured parts. The process relies on the dual polymerization reactions of OSTE+ polymers, where the first curing step is used in OSTE+RIM for molding intermediately polymerized parts with well-defined shapes and reactive surface chemistries. In the facile back-end processing, the replicated parts are directly and covalently bonded and become fully polymerized using the second curing step, generating complete microfluidic devices. To achieve unprecedented rapid processing, high replication fidelity and low residual stress, OSTE+RIM uniquely incorporates temperature stabilization and shrinkage compensation of the OSTE+ polymerization during molding. Two different OSTE+ formulations were characterized and used for the OSTE+RIM fabrication of optically transparent, warp-free and natively hydrophilic microscopy glass slide format microfluidic demonstrator devices, featuring a storage modulus of 2.3 GPa and tolerating pressures of at least 4 bars.

Abstract-This paper presents a concept for the wafer-scale manufacturing of microactuators based on the adhesive bonding of bulk shape memory alloy (SMA) sheets to silicon microstructures. Wafer-scale integration of a cold-state deformation mechanism is provided by the deposition of stressed films onto the SMA sheet. A concept for heating of the SMA by Joule heating through a resistive heater layer is presented. Critical fabrication issues were investigated, including the cold-state deformation, the bonding scheme and related stresses and the TitaniumNickel (TiNi) sheet patterning. Novel methods for the transfer stamping of adhesive and for the handling of the thin TiNi sheets were developed, based on the use of standard dicing blue tape. First demonstrator TiNi cantilevers, wafer-level adhesively bonded on a microstructured silicon substrate, were successfully fabricated and evaluated. Intrinsically stressed silicon dioxide and silicon nitride were deposited using plasma enhanced chemical vapor deposition to deform the cantilevers in the cold state. Tip deflections for 2.5 mm long cantilevers in cold/hot-state of 250/70 µm and 125/28 µm were obtained using silicon dioxide and silicon nitride, respectively. The bond strength proved to be stronger than the force created by the 2.5 mm long TiNi cantilever and showed no degradation after more than 700 temperature cycles. The shape memory behavior of the TiNi is maintained during the integration process.Index Terms-Adhesive bonding, blue tape, contact printing, microactuator, microelectromechanical systems (MEMS), nitinol, shape memory alloy (SMA), stress layers, titanium-nickel (TiNi), integration, transfer stamping, wafer-scale integration, wet etching.

PostprintThis is the accepted version of a paper published in Sensors and actuators. B, Chemical. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination.Citation for the original published paper (version of record):Pardon, G., Ladhani, L., Sandström, N., Ettori, M., Lobov, G. et al. [Year unknown!] Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface. Sensors and actuators. B, Chemical AbstractIn this work, the development of a point-of-care (PoC) system to capture aerosol from litres of air directly onto a microfluidic lab-on-chip for subsequent analysis is addressed. The system involves an electrostatic precipitator that uses corona charging and electrophoretic transport to capture aerosol droplets onto a microfluidic air-to-liquid interface for downstream analysis. A theoretical study of the governing geometric and operational parameters for optimal electrostatic precipitation is presented. The fabrication of an electrostatic precipitator prototype and its experimental validation using a laboratory-generated aerosolized dye is described. Collection efficiencies were comparable to those of a state-of-the-art Biosampler impinger, with the significant advantage of providing samples that are at least 10 times more concentrated. Finally, we discuss the potential of such a system for breath-based diagnostics.