A patented HµREL® microfluidic circuit comprises an arrangement of separate but fluidically interconnected “organ” or “tissue” compartments. Each compartment contains a culture of living cells drawn from, or engineered to mimic the primary function(s) of, the respective organ or tissue of a living animal. Microfluidic channels between the compartments permit a culture medium that serves as a “blood surrogate” to re-circulate as in a living system. Drug candidates of interest are added to the culture medium and allowed to re-circulate through the device; they then distribute to and interact with the cells in the organ compartments much as they would in the human body. The effects of drug compounds and their metabolites on the cells within each respective organ compartment are detected by measuring or monitoring key physiological events. The cell types employed may be adherent or non-adherent, and derived from either standard cell culture lines or primary tissue.

The physical features of a HµREL embody parametric values derived from a physiologically-based pharmacokinetic (“PBPK”) model. The geometry and fluidics of the device are fashioned to stimulate the values for drug residence time, circulatory transit time, organ cell density, tissue size, shear stress, and certain other physiological parameters found in the living animal, so as to mimic the fluid-mediated interactions of the organ systems represented in the microfluidic circuit.

HµREL's technology is hospitable to numerous experimental applications, and compatible with virtually any type of traditional in vitro assay modality (immunohistochemical, immunofluorescent, and others). Embodied in standard, micro-titer array format, HµRELs are intended for “plug-and-play” compatibility with plate readers and other standard laboratory instruments, and their use can be automated for increased throughput and improved reproducibility.