The other end of the spectrum from detecting bio-signatures of life on individual planets, would be mega structures.
Once a civilization began harvesting the energy of a few star systems, it would have a good chance of colonizing their whole galaxy in a blink of an eye.
(100 thousand years, plus or minus an order of magnitude, as compared to universe time in billions of years.)
So we would be much more likely to see totally colonized galaxies, rather than partially colonized.
I would be curious about which instruments would detect infra-red galaxies, I.e. galaxy sized objects where all starlight was put to use, with only infra-red light as waste.
And would that be an object that would stand out if a major telescope came across it, or require specific initiative to search and find?
And speaking of optics, is there any reason to suspect an efficient civilization would leak lower frequency light than infra-red?