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.
Microfluidics is assumed to be one of the leading and most promising areas of research since the early 1990s. In microfluidic systems, small spherical magnetic particles with superparamagnetic properties, called magnetic beads, play an important role in the design of innovative methods and tools, especially in bioanalysis and medical sciences. The intention of this review paper is to address main aspects from the state-of-the-art in the area of magnetic bead research, while demonstrating the broad variety of applications and the huge potential to solve fundamental biological and medical problems in the fields of diagnostics and therapy. Basic issues and demands related to the fabrication of magnetic particles and physical properties of nanosize magnets are discussed in Section 2. Of main interest are the control and adjustment of the nanoparticles’ properties and the availability of adequate approaches for particle detection via their magnetic field. Section 3 presents an overview of magnetic bead applications in nanomedicine. In Section 4, practical aspects of sample manipulation and separation employing magnetic beads are described. Finally, the benefits related to the use of magnetic bead-based microfluidic systems are summarized, illustrating ongoing questions and open tasks to be solved on the way to an approaching microfluidic age.
The absorption of dietary calcium through the intestinal barrier is essential for maintaining health in general and especially of the bone system. We propose a microfluidic model that studies free calcium (Ca 2+ ) transport through a confluent monolayer of Caco-2 cells. The latter were cultured on a porous membrane that was positioned in between a top and bottom microfluidic chamber. Fresh cell culture medium was continuously supplied into the device at a flow rate of 5 nL s À1 and the culture progress of the cell monolayer was continuously monitored using integrated Transepithelial Electrical Resistance (TEER) electrodes. The electrical measurements showed that the Caco-2 monolayer formed a dense and tight barrier in 5 days. The transported free Ca 2+ from the top microfluidic chamber to the basolateral side of the cell monolayer was measured using the calcium-sensitive dye fura-2. This is a ratiometric dye which exhibits an excitation spectrum shift from 340 nm to 380 nm, when it binds to Ca 2+ with an emission peak at 510 nm. Therefore, the concentration of free Ca 2+ is proportional to the ratio of fluorescence emissions obtained by exciting at 340 nm and 380 nm. The barrier function of the cell monolayer was evaluated by a measured rate of Ca 2+ transport through the monolayer that was 5 times lower than that through the bare porous membrane. The continuous perfusion of cell nutrients and the resultant mechanical shear on the cell surface due to the fluid flow are two key factors that would narrow the gap between the in vivo and in vitro conditions. These conditions significantly enhance the Caco-2 cell culture model for studying nutrients bioavailability.
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