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I think the current replacement for 3.5" style drives is done with the U.2 connector / form factor (?). https://en.wikipedia.org/wiki/U.2

Not sure if anyone has maximized the space like you're thinking however.

I think all the record-setting high capacity drives have moved over to EDSFF E1.L "Ruler" form factor, though I'd also expect 64+TB drives to be offered in EDSFF E3 sizes that are the more direct successors to U.2/U.3 2.5" form factors.

TIL! Maybe I'll have a "EDSFF E1.L" in my homelab someday :)

Heat's going to be an issue, but I guess if the 3.5 enclosure was skeletal or otherwise provided adequate heatsinking, it'd be okay.

I'd worry about heat issues doing that.