[ytNumbers]

Pick an upstairs room to do your work in. Put a big sign on the door that says you may only knock on the door if the house is on fire. When you're ready for a break from working on your project, then open the door. Anyone who ignores the sign gets an immediate "Hey! Can't you read?!!"

[throwawayIn2019]

Maybe we can put an addition on our house to make it a work space or move the kids to the addition and use their bedroom as my work space. It has an insanely large window and overlooks the lake.

[tomasdore]

Perhaps the answer is as simple as an extension for you to work in, which is set up as an airlock-style system of doors, so that you are not really disturbable by your wife. I mean simply three or more doors in a row, with a little gap between each. A den, if you prefer. Or an inner sanctum. It is at least worth a good try.