The space agency has been struggling to locate the source of a tiny leak in the space station since September 2019, when it noticed that the cabin was letting out more air than would be expected.
In the months since, it has been unable to locate the problem that could be causing the small drop in pressure.
Nasa has also noticed that the rate of the depressurisation has increased, though the leak still remains within specifications.
The leak poses no risk to either the station or the people living on board. The space station can be repressurised using nitrogen tanks that are taken to the space station on cargo missions.
But Nasa hopes that isolating the problem will finally allow it to be fixed and allow the space station to return to normal operation.
The test will see the three crew members who are currently in the floating lab spend their weekend inside the Russian part of the space station.
The Zvezda service module served as the living quarters when permanent habitation of the space station began in 2000, and they will still have access to the Soyuz ship that delivered them to the ISS and will take them home.
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All the hatches on the space station will be closed during the test, so that engineers can monitor the air pressure in each module.
That should allow them to isolate the problem module, and further investigations will allow for the potential repair of the problem.
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