Hurel -- an in vivo-surrogate assay platform for cell-based studies

Abstract

Accurate prediction of the human response to potential pharmaceuticals is difficult, often unreliable, and invariably expensive. Traditional in vitro cell culture assays are of limited value, because they do not accurately mimic the complex environment to which a drug candidate is subjected within the human body. While in vivo animal studies can account for the complex inter-cellular and inter-tissue effects not observable from in vitro assays, animal studies are expensive, labour intensive, time consuming, and unpopular. In addition, there is considerable concern as to whether animal studies can predict human risk sufficiently precisely, because, first, there is no known mechanistic basis for extrapolation from high to low doses, and second, cross-species extrapolation has frequently been found to be problematic with respect to toxicity and pharmacokinetic characteristics. To address these limitations, an interactive, cell-based microfluidic biochip called a Hurel was developed. The Hurel system consists of living cells segregated into interconnected "tissue" or "organ" compartments. The organ compartments are connected by a re-circulating culture medium that acts as a "blood surrogate". The fluidics are designed so that the primary elements of the circulatory system, and more importantly, the interactions of the organ systems, are accurately mimicked. Drug candidates are exposed to a more-realistic animal or human physiological environment, thus providing a higher and more accurate informational content than can the traditional in vitro assays. By affording dynamic assessment of potential toxicity, metabolism, and bioavailability, the device's capabilities hold the potential to markedly improve the prioritisation of drug leads prior to animal studies.