Lake Ellsworth lies below ice that is at least two miles (3.2 km) thick.
Its pitch-black waters have remained isolated and unseen for up to half a million years.
This will be the first attempt to extract uncontaminated samples of water and sediment from a body of water so far below the surface.
The investigation is part of a search to understand the limits of where life is possible and, despite the high pressures and lack of sunlight, it is likely that microbes will be detected.
The lake is about 14 km long, 3 km wide and 160 m deep – about the size of Lake Windermere, England’s largest.
In a region of Antarctica notorious for its low temperatures and near-constant winds, operating at this location is a huge challenge.
The project is made all the tougher because of the need for all the equipment to be kept sterile throughout the process.
The team behind the £8m project is readying a hot-water drill that will be used to blast a hole from the surface of the ice all the way down to the lake.
The chief scientist, Professor Martin Siegert of Bristol University, said he had first thought of exploring sub-glacial lakes 16 years ago.
“We’re very excited about this work and we’re very much looking forward to doing science that has taken us so long to plan.
“The first challenge was to develop the equipment and we’ve done that. The second was to keep it clean and we’ve done that. The third was to get it to Antarctica in a clean way and we’ve done that too.
“Now the experiment is set we can hit the Go button.”
A small mountain of 270,000 litres of snow is ready to be shoveled into boilers – the first of a vast quantity needed to produce enough water for the operation.
The water will be filtered to remove any microbes, then screened through ultra-violet light before being heated to 90 degrees C and passed into the drill which will melt a passage through the ice-sheet.
The hot water pipes connecting the boilers have been insulated and in some cases fitted with heating devices. All the key component are wired to relay data. And the drill hose, which is 3.4 km long, has been cleaned and checked.
The drilling operation is expected to last five days and the bore-hole is projected to remain open for no more than 24 hours.
During this brief window, the plan is to lower a sampling probe fitted with HD cameras to gather the first images of the lake and collect water samples.
Next the team hopes to lower a second device which will settle on the bed of the lake and extract a core of the sediment – which should provide an invaluable record of the history of the lake and reveal when it was covered by ice.
Project manager Chris Hill of the British Antarctic Survey described the “funny feeling” of planning the project for so long and now being ready.
In his blog, he wrote:
“The twelve people here have sat around a meeting table on many occasions during that period…but now, for the first time, we are together in Antarctica, at Lake Ellsworth, with all the equipment, as a team and we have to make it happen.
“No pressure then!”
Earlier this year Russian scientists extracted samples from a much larger Antarctic lake, Lake Vostok, though there are questions about the risks of contamination.
And an American team reported last month on the discovery of microbes in Lake Vida, but from far shallower depths than the waters of Lake Ellsworth.
The initial findings of the Lake Ellsworth project should be known in about a week’s time.
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