Rosalinda Hardiman will brave freezing waters, jellyfish and seasickness as she swims for up to 20 hours across one of the world's busiest shipping lanes – using just her arms.
The 56-year-old is determined to join an elite handful of disabled people who have completed the gruelling challenge, to prove to herself and others just what can be achieved.
She said: 'This is a long-term dream. There is a lot of prejudice in swimming once people look at the wheelchair.
'Perhaps by doing this I will be waving the flag to say "do not discount us – we may not be able to walk to the shops or run for the bus but there is a lot we can do".'
Ms Hardiman was struck down by polio when she was just six, and by the time she was a teenager she had very limited movement in her legs.
After a string of painful operations she was left with leg calipers and in a wheelchair, but the collections manager for Portsmouth's city museum has never let it stop her.
Ms Hardiman, of Byron Road, Copnor, started swimming in the sea after moving to Portsmouth in 1980.
But she soon discovered a talent for racing in pools, and went on to become a medal-winning paralympian.
Just after the Sydney Olympics a driver reversed into her stationary car as she was reaching to get something from the glove box, injuring her shoulder and ending her competitive-pool swimming career, forcing her to return to open-water swimming.
Already she has swum the English Channel in a relay team of six, and she recently swam the length of Lake Windermere.
Ms Hardiman said: 'This is the big one for me. I have never done anything like this before.
'For a long time I didn't know how to go about doing it.
'Being disabled means I am a little bit shy of new things, having been brushed off so many times in the past.
'Even though I now have a full-time job and a fully independent life, I still feel the need to prove myself.'
Ms Hardiman was due to set off tomorrow, but bad weather means she is waiting for an opportunity to travel to Dover to start the challenge – which could be any day.
She said: 'I am nervous. I don't really like jellyfish having been stung before.
'But no matter how awful it is while I am doing it, I just want to do this.'