Multi-Organ Microdevice

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Invention Summary The invention relates to a microfluidic-based body-on-a-chip device that comprises single-organ chips or discs which can be assembled at will. The design of this device allows for independent maturation of the tissue cells (modularity of the chips) and for unidirectional re-circulation of the liquid medium via for example a new passive valve. Technology Overview Multi-organ microphysiological systems have been developed to mimic the human metabolism in microfluidic devices. Called, body-on-a-chip system, it enables to study the reaction of miniature organs (culture of tissue cells in a chip) to the same environment (media) and the interaction between each other. The aim is to evaluate drug candidates in terms of toxicity, efficacy and delivery. The present device developed at Cornell University addresses limitations of current body-on-a-chip systems: The dependence on the use of an external or integrated micro-pump, which renders the system difficult to maintain at long term (bubble formation and cost); The use of less media thus less growth factors, nutrients, etc.; A recirculating media system that allows creating an adequate growing environment for each tissue and preserving the functionality of the tissues (shear stress). Cornell researchers have designed a pumpless microfluidic platform that allows stacking multiple single-organ chips into a microdevice. The advantage of this design is multiple: (i) it enables to grow each tissue cells separately; (ii) it allows gravity-driven fluidic flow and passive fluid controls via hydraulic resistant of the microfluidic channel network (Fig. 1.3); (iii) unique, newly valve designs prevent the liquid medium from flowing backwards through capillary forces (Fig. 1.3). 1.1) Modular device design with 2 organ chips 1.2) Cross section of the device 1.3) Schematic of the operation of the passive valve and fluidic flow Proof-of-concept: The microdevice has been assessed by co-culturing GI tract tissue and liver tissue under uni-directional flow. It has been demonstrated that both cell cultures retained their viability (AST concentration). The overall GI tract layer preserved its barrier function (TEER measurement), the liver tissue exhibited high metabolic activity (albumin and urea synthesis) and its ability to protect against toxic substance (CY enzymatic activity). Potential Applications Drug testing in co-culture (toxicity, efficacy and delivery) Adaptable to high throughput screening. Advantages Easy, leak-free and air bubble-free assembly of microfluidic devices Inexpensive and easy to use Allows for co-culture of tissue in vitro Allows for independent tissues maturation and suitable to study cell lines that reach confluency at different time Unidirectional flow eliminating fluid shear thus suitable to culture barrier tissues that are sensitive to the direction of the shear Allows for personalize design of systems with multiple organ settings by stacking of single-organ chips System can be singular or adapted to fit multiple well plates.