This focus article introduces the concept of NutriChip, an integrated microfluidic platform for investigating the potential of the immuno-modulatory function of dairy food. The core component of the NutriChip is a miniaturized artificial human gastrointestinal tract (GIT), which consists of a confluent layer of epithelial cells separated from a co-culture of immune cells by a permeable membrane. This setting creates conditions mimicking the human GIT and allows studying processes that characterize the passage of nutrients though the human GIT, including the activation of immune cells in response to the transfer of nutrients across the epithelial layer. The NutriChip project started by developing a biologically active in vitro cellular system in a commercial Transwell co-culture system. This Transwell system serves as a reference for the micro-scale device which is being developed. The microfluidic setup of NutriChip allows monitoring of the response of immune cells to pro-inflammatory stimuli, such as lipid polysaccharide (LPS), and to the application of potentially anti-inflammatory dairy food. This differential response will be quantified by measuring the variation in expression of pro-inflammatory cytokines, including interleukin 1 (IL-1) and interleukin 6 (IL-6), secreted by the immune cells, and this is achieved by using a dedicated optical imager. A series of dairy products will be screened for their anti-inflammatory properties using the NutriChip system and, finally, the outcome of the NutriChip will be validated by a human nutrition trial.Therefore, the NutriChip platform offers a new option to evaluate the influence of food quality on health, by monitoring the expression of relevant immune cell biomarkers.

We have developed a flexible-substrate-based three-axial force sensor, composed of finger-shaped electrode capacitors, whose operation is based on the measurement of a capacitance change induced upon applying a three-axial load. The electrode design supports high sensitivity to shear forces. An overall flexibility of the sensor and elasticity of the capacitor's dielectric is obtained by integrating three polymers in the sensor's technology process, namely polyimide, parylene-C, and polydimethylsiloxane, combined with standard metallization processes. We have theoretically modeled the sensor's capacitance and its three-axial force sensitivity. The unit capacitors have static capacitances in the range of 20 pF. The electro-mechanical characterization of the capacitors reveals in the normal direction a sensitivity Sz = 0.024 kPa−1 for pressures <10 kPa, whereas for higher pressures the measured sensitivity Sz = 6.6 × 10−4 kPa−1. Typical measured shear force sensitivity Sx = 2.8 × 10−4 kPa−1. These values give our transducer high potential for use in skin-like sensing applications.

We study the droplet-based synthesis of fluorescent silica nanoparticles (50-350 nm size) in a microfluidic chip. Fluorescein-isothiocyanate (FITC) dye is first chemically linked to aminopropyl triethoxysilane (APTES) in ethanol and this reaction product is subsequently mixed with tetraethyl orthosilicate (TEOS) to yield a fluorescent silicon alkoxide precursor solution. The latter reacts with an aqueous ethanol-ammonia hydrolysing mixture inside droplets, forming fluorescent silica nanoparticles. The droplets are obtained by pinching-off side-by-side flowing streams of alkoxide solution/hydrolysing mixture on a microfluidic chip using a Fluorinert oil continuous phase flow. Synthesis in droplets leads to a faster reaction and allows drastically improved nanoparticle size uniformity (down to 3% relative standard deviation for 350 nm size particles) when compared to conventional bulk synthesis methods, thanks to the precise control of reagent concentrations and reaction times offered by the microfluidic format. Incorporating FITC inside silica nanoparticles using our method leads to reduced dye leakage and increases the dye's stability, as evidenced by a reduced photochemical bleaching compared to a pure FITC solution.

We report on in vivo temperature measurements performed in mice at two specific sites of interest in the animal body over a period of several hours. In particular, the aim of this work was to monitor mouse metabolism during cold exposure, and to record possible temperature differences between the body temperature measured in the abdomen and the temperature of the brown adipose tissue (BAT) situated in the interscapular area. This approach is of biological interest as it may help unravelling the question whether biochemical activation of BAT is associated with local increase in metabolic heat production. For that purpose, miniaturized thermistor sensors have been accurately calibrated and implanted in the BAT and in the abdominal tissue of mice. After 1 week of recovery from surgery, mice were exposed to cold (6 °C) for a maximum duration of 6 h and the temperature was acquired continuously from the two sensors. Control measurements with a conventional rectal probe confirmed good performance of both sensors. Moreover, two different mouse phenotypes could be identified, distinguishable in terms of their metabolic resistance to cold exposure. This difference was analyzed from the thermal point of view by computational simulations. Our simple physical model of the mouse body allowed to reproduce the global evolution of hypothermia and also to explain qualitatively the temperature difference between abdomen and BAT locations. While with our approach, we have demonstrated the importance and feasibility of localized temperature measurements on mice, further optimization of this technique may help better identify local metabolism variations.

We introduce a new low-temperature (280 °C) parylene-to-SiO2 bonding process with high device yield (>90%) for the fabrication and integration of high-pressure-rated microfluidic chips. Pull tests demonstrate a parylene-to-SiO2 bonding strength of 10 ± 3 MPa. We apply this technique for bonding Pyrex and silicon wafers having multiple metal layers to fabricate standard packaged microfluidic devices. By performing electrochemical impedance spectroscopy of electrolyte solutions in such devices, we demonstrate that electrodes remain functional after the etching, bonding and dicing steps. We also develop a high-pressure microfluidic and electrical integration technology, eliminating special fluidic interconnections and wire-bonding steps. The burst pressure of the integrated system is statistically shown to be 7.6 ± 1.3 MPa, with a maximum achieved burst pressure of 11.1 MPa, opening perspectives for high-pressure applications of these types of microfluidic devices.