EZ Cap Reagent AG Additional applications for organ on

Additional applications for organ-on-a-chip devices are expansive, including the assessment of environmental toxin (National Academies, 2014), modeling of disease progression and treatment (Bhatia and Ingber, 2014; Huh et al., 2012), the advancement of personalized medicine through the improvement of screening and monitoring diagnostics (Neuzi et al., 2012; Schumacher et al., 2012), and even the development of vaccines to counter bioterrorism (Wang, 2004). The increased use of organ-on-a-chip devices in various fields can ultimately lead to improved pharmaceutical, health and regulatory decisions. The following section will discuss some of the existing technologies for the in vitro modeling of barrier EZ Cap Reagent AG on chips.
Current Technologies in Chip Design/Culturing Methods
Advantages Over Current Methods The use of microfluidic-based in vitro modeling has many advantages over traditional testing methods for clinical studies. In comparison to static in vitro culture, microfluidics allow for dynamic fluid flow through cultures. This highly controlled dynamic cell growth environment has been linked to increased cell growth, differentiation, and polarization, allowing for more in vivo-like tissue growth and behavior (Jang et al., 2011). Additionally, fluid flow enables ADMET properties, allowing for more accurate predictions of physiologically based pharmacokinetic (PBPK) properties than with static systems. The combination of microfluidics with this in silico modeling has the possibility for more accurate efficacy and toxicity predictions (Fig. 4). Fluid flow has also been linked with longer culture periods, up to a month as shown in microfluidic modeling of lung tissue (Huh et al., 2010). This allows for more clinically relevant time scales as many diseases develop over chronic exposure, or can take time to express symptoms. Microfluidics by definition also utilize smaller media volumes than static cultures in wells, using only a fraction of the volume of traditional cultures over the same area of cells. This ratio of fluid to tissue is a closer match to that found in the body, and leads to a smaller reagent requirement, reducing cost and maximizing information obtained from valuable samples early on in the drug development process. Finally, microfluidic chambers allow for the possibility of tissue/organ interconnection. Fluidic chambers can be connected to one another, allowing for a degree of fluidic interaction and cell signaling while maintaining physical separation, an application that is not currently possible in static cultures. Microfluidic in vitro modeling also has many advantages over in vivo animal studies. One of the greatest flaws in animal testing is the questionable correlation of animal data to human systems. This often results in either a lack of efficacy or unexpected toxicity when transitioning from animal studies to human clinical trials. The use of in vitro microfluidic devices has the potential to overcome this issue through the use of human cells or tissues (in the case of tissue explants) in physiologically relevant microenvironments. By matching the growth environment of these tissues within a microfluidic device, it is possible to observe potential drug interactions as they would translate to human systems, potentially allowing for much better drug efficacy and toxicity predictions. Additionally, imaging is much simpler in microfluidics due to the transparent nature of many fabrication materials, and the control of tissue and cell positioning which is not possible in living systems. This allows for real time imaging under flow without disrupting cell growth. Microfluidics also allow for high throughput sample processing and more realistic sample sizes than with animal studies, where it can be time consuming and expensive to obtain a large sample of animal specimens. This throughput is perhaps one of the greatest advantages of the use of microfluidic technologies. Through the use of multi-organ systems like those described in this paper, it is possible to simultaneously assess the effects or toxicity of drugs and their metabolites on multiple tissue types, further reducing testing times. This type of high throughput analysis can allow for rapid, inexpensive and highly efficient testing. Additionally, it is possible to incorporate systems to monitor tissue and barrier health (TEER, automatic sampling, etc.) within these engineered devices, streamlining the testing process even further. Finally, many pathologies of toxicity and disease are poorly understood on molecular and biochemical levels which are challenging if not impossible to observe at the macro scale within a living system. Microfluidics offer an alternative at a small enough scale, where cell–cell or cell–tissue interactions can be simplified and accurately emulated, allowing for easily observable interactions.