Methods, systems and compositions for functional in vitro cellular models of mammalian systems

A method of assessing one or more effects of varying an input variable or a cell culture characteristic on a microfluidic cell culture analog system, the method comprising:

• varying an input variable or a cell culture characteristic to which a microfluidic cell culture analog system is exposed, the microfluidic cell culture analog system comprising one or more organ components, each organ component comprising one or more chambers, and each organ component (i) being microfluidically coupled to one another, and (ii) comprising cells cultured on a surface;
• recording, over a duration of time, changes in measured electrophysiological properties, contractile properties or both in response to the varying input variable or cell culture characteristic;
• in which the electrophysiological properties, if measured, are measured from a first population of cells cultured on a surface comprising a microelectrode array housed in a first chamber and the contractile properties, if measured, are measured from a second population of cells cultured on a surface comprising a cantilever array housed in a second chamber;
• the recorded changes providing an assessment of the one or more effects of varying an input variable or a cell culture characteristic.

A method of assessing one or more effects of a metabolism of an input variable using a microfluidic cell culture analog system, the method comprising:

• providing the microfluidic cell culture analog system,
• contacting liver cells of a hepatic component of a microfluidic cell culture analog system with an input variable under conditions in which the liver cells at least partially metabolize the input variable into one or more hepatic metabolites, the microfluidic cell culture analog system comprising multiple microfluidically coupled organ components, including a hepatic component and at least a first and second other organ components;
• allowing the input variable and the one or more hepatic metabolites to flow through the microfluidic cell culture analog system;
• recording, over a duration of time, changes in simultaneously measured electrophysiological and contractile properties in response to the input variable and the one or more hepatic metabolites;
• in which the electrophysiological properties are measured from a first population of cells cultured on a microelectrode array of a first organ component and the contractile properties are measured from a second population of cells cultured on a cantilever array of a second organ component;
• the recorded changes providing an assessment of the one or more effects of the metabolism of the input variable.

A method of dynamically controlling a microfluidic cell culture analog system, the method comprising:

• measuring at least one electrophysiological property from a first population of cells cultured on a microelectrode array of a first organ component of a microfluidic cell culture analog system comprising multiple microfluidically coupled organ components;
• simultaneously measuring at least one contractile property from a second population of cells cultured on a cantilever array housed in a second chamber;
• recording changes in the simultaneously measured electrophysiological and contractile properties over a duration of time;
• and
• altering one or more input parameters or cell culture characteristics of the microfluidic cell culture analog system in response to the recorded changes, thereby exerting dynamic control over the microfluidic cell culture analog system.