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    • We must also consider the availability of

    2018-10-23

    We must also consider the availability of relevant human cells. It can be difficult to obtain healthy primary sirtuins from a diverse population, so an alternative must be considered. Recently, it has been suggested that human induced pluripotent stem cell technologies could be utilized to provide relevant cell models, additionally establishing the possibility for personalized medicine (Williamson et al., 2013; Bellin et al., 2012). Cell availability is not only an issue with healthy tissue modeling, but must also be considered in disease modeling. Can a cell phenotype be discerned that represents the pathophysiology of underlying diseases? Further along this avenue, can a phenotype be altered in vitro in such a way that potential therapies might emerge? Another imperative question is whether it will be possible to develop a universal blood substitute for microfluidic culturing (Schaffner et al., 1995; Guo et al., 2011). Currently used media have been optimized for specific cell types, but in order to see tissue–tissue interactions in more complex multi-organ chamber devices, it will be necessary to have a universal solution that will equally supplement multiple cell types. The papers referenced earlier in this review that incorporated multiple cell/tissue types into multi-chamber devices faced this very issue and offer potential models to solve these problems. Questions pertaining to device fabrication materials have also been of recent concern. There has recently been a push toward thermoplastic materials (polystyrene, cyclic olefin copolymer, polymethyl methacrylate, polycarbonate) over elastomers (PDMS), which are used in the majority of organ-on-a-chip devices because of their low cost, high availability and ease of use in soft lithography. Recent studies have determined that elastomer materials can leach uncrosslinked oligomers into solution, absorb small molecules (affecting cell signaling, and pharmaceutical dosage), and have higher vapor permeability (evaporation can lead to detrimental effects on micro- and nanoliter fluid volumes) (Toepke and Beebe, 2006; Regehr et al., 2009). Finally, when considering device design, it is important to ask: What types of real-time detection and analysis can be incorporated into chip devices? Many of the works described in this review have incorporated TEER, and fluorescent or optical based measurements, however many recent advances in label-free protein assays have been reported. Electrical biosensors and automated sampling for label-free detection of protein and disease biomarkers have proven to be useful, however their incorporation into chip systems has not yet been investigated (Luo and Davis, 2013). Additionally, the use of universal assays will need to be incorporated at a larger scale. Current assays generally focus on cell function and behavior, but organs and tissues also need to be evaluated at a functional level. As an example, Stancesu et al. monitored the contractile stress of human cardiomyocytes and used Multi-electrode arrays (MEAs) to measure electrical activity in an in vitro model of the heart. This data, coupled with cell-based assays could provide relevant predictions for drug toxicity and efficacy ranging from cell–cell to systemic scales (Stancescu et al., 2015). It is also important to consider, when designing these monitoring and testing methods that with low cell culture volume and cell count compared to traditional culturing, it might be difficult to detect biological signals at this scale. These sensors will be required to have high sensitivity to detect changes in biological responses. Ultimately, the main question to be asked is: which is more important, complexity or practicality? It may, in the future, be possible to design whole-body microfluidics that can account for systemic organ interactions and signaling, and parallel the function of the human body, but would this sort of system be practical? The more intricate the device becomes, the more difficult it becomes to manufacture, distribute, and train operators. A reason balance between these two opposing forces must be reached in order for the creation of a practical, yet insightful technology to be widely utilized.