A versatile pumpless multi-channel fluidics system for maintenance and real-time functional assessment of tissue and cells

Summary: To address the needs of the life sciences community and the pharmaceutical industry in pre-clinical drug development to both maintain and continuously assess tissue metabolism and function with simple and rapid systems, we improved on the initial BaroFuse to develop it into a fully functional, pumpless, scalable multi-channel fluidics instrument that continuously measures changes in oxygen consumption and other endpoints in response to test compounds. We and several other laboratories assessed it with a wide range of tissue types including retina, pancreatic islets, liver, and hypothalamus with both aqueous and gaseous test compounds. The setup time was less than an hour for all collaborating groups, and there was close agreement between data obtained from the different laboratories. This easy-to-use system reliably generates real-time metabolic and functional data from tissue and cells in response to test compounds that will address a critical need in basic and applied research. Motivation: There is a critical need for developing in vitro methods that provide mechanistic insight at the tissue and intracellular levels as well as to reduce the need for in vivo studies. Flow culture is recognized as superior to static for both maintenance and assessment of tissue, as static systems are unable to maintain viability of most tissue preparations that are not cellular monolayers. However, technical challenges and a need for increased amounts of biological samples are impediments to their routine use in the majority of laboratories in the life sciences. We have addressed these two issues by developing a simple-to-use flow system that utilizes gas pressure instead of peristaltic or syringe pumps to drive multi-channel microflow. The delivery of steady flow over a wide range of flow rates enables small amounts of tissue to be maintained and assessed.