Closed-loop perfusion circuit for cell and tissue cultures

A closed-loop perfusion system comprising:

• a sealed biological culture container configured to house a biological cell culture;
• a filtering unit wherein the filtering unit comprises a semi-porous membrane that permits passage of waste products from an output of the sealed biological cell culture container and permits passage of nutrients from a nutrient media solution but blocks passage of beneficial molecules from the output of the sealed biological cell culture container;
• a first fluid path between the sealed biological cell culture container and the filtering unit, wherein the first fluid path connects the output of the sealed biological cell culture container to an input of the filtering unit;
• a second fluid path between the sealed biological cell culture container and the filtering unit, wherein the second fluid path connects an output of the filtering unit to an input of the sealed biological cell culture;
• a first pump that delivers a mixture of the nutrient media solution and the beneficial molecules output by the sealed biological cell culture container to the sealed biological culture container through the second fluid path and delivers the output of the sealed biological cell culture container to the filtering unit through the first fluid path;
• a multielectrode array (MEA) contained within the sealed biological culture container, the MEA comprising:
• a plurality of biological neurons disposed on the MEA;
• and
• one or more sensors to measure electrical signals output by one or more of the plurality of biological neurons;
• and
• a computer coupled to the MEA, wherein the computer is configured to:
• output a command to provide a reward stimulus to the contents of the sealed biological culture container responsive to a digital input signal from the MEA.