Device and method for measuring in-cell protein folding

A system comprising:

• a plate with a plurality of open wells;
• an incubator comprising:
• a frame defining a recess configured to receive the plate with the plurality of open wells and to removably accommodate the plate in the recess;
• a removeable cover for the recess, wherein the cover is transparent to laser light of a first wavelength and wherein the cover encloses the recess so that a controlled environment is established in the recess for preserving function of cells cultured in the plurality of wells, wherein the controlled environment encompasses the plurality of open wells and a region of the recess defined between the plate and the frame;
• an environmental supply coupled to the controlled environment and configured to supply heat and a gas mixture including carbon dioxide and water vapor to the controlled environment including the plurality of open wells and the region of the recess defined between the plate and the frame;
• and
• for each well of the plurality of wells, a plurality of perfusion tubes disposed to dispense fluid to or from a distal end at a position of each well,
• wherein each perfusion tube of the plurality of perfusion tubes is configured at a proximal end to be connected in fluid communication with one of a plurality of corresponding reservoirs outside the incubator;
• a laser source configured to emit a laser beam at the first wavelength;
• the environmental supply comprising;
• a thermal source configured to supply the heat to the controlled environment;
• and
• a gas source configured to supply the gas mixture;
• the plurality of corresponding reservoirs;
• a plurality of pumps in fluid communication with the plurality of corresponding reservoirs;
• at least one processor;
• and
• at least one memory including one or more sequences of instructions,
• the at least one memory and the one or more sequences of instructions configured to, with the at least one processor, cause the at least one processor to control on or more components of a group of components comprising the laser, the thermal source, the gas source, and the plurality of pumps;
• wherein the at least one memory and the one or more sequences of instructions are further configured to, with the at least one processor, cause the at least one processor to perform at least the steps of:
• a. for a first time interval, operate at least one first pump of the plurality of pumps to perfuse each well with fluid from a first reservoir of the plurality of corresponding reservoirs;
• b. for a second time interval after the first time interval operate at least one second pump of the plurality of pumps to perfuse each well with fluid from a different second reservoir of the plurality of corresponding reservoirs;
• c. for a third time interval after the second time interval operate at least one third pump of the plurality of pumps to perfuse a first well of the plurality of wells with fluid from a different third reservoir of the plurality of corresponding reservoirs;
• d. for a fourth time interval after the third time interval operate the laser source to illuminate the first well with the laser beam at the first wavelength;
• e. after the fourth time interval operate at least one fourth pump of the plurality of pumps to perfuse the first well with fluid from a different fourth reservoir of the plurality of corresponding reservoirs.