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Well lets look at the options - Looking at Motive, Resources, and Means to create a world ending mutagen bomb.
Barring an unknown enemy, that leaves us 2 known and 1 potential enemy + 1 wild card option.
Kraang
Baxter Stockman
EPF
Donatello
Kraang have certainly, means, resources and motive to commit such an act, but their hivemind was - so far as we are aware - crippled by the death of Kraang Prime at the hands of the Triceratons. The Kraang should no longer be a threat at all, though its possible Kraang enclaves still exist under different leadership like Sub Primes.
Baxter has a strong motivation to try and make himself a mutant again, and the comics (and 1 episode) have indicated a desire to mutate others to use as slaves/servants. He certainly has the technical expertise to create both the weapon and to program the mutagen. Given the mutagens seemingly ad hoc choice of animal DNA to splice - it suggests access to a menagerie and stockpiles of animal DNA. Something Baxter is also known to have had. So far as resources go, though he relied on Shredder, Shredders resources didn't vanish with him. Baxter could easily have taken what he needed - including a massive stockpile of mutagen Shredder was known to have had.
The EPF salvaged multiple examples of kraang tech and equipment. This likely included mutagen. They could have sought to weaponize it but this does seem against their modus operandum. However the EPF has been shown to be corrupted before. They have at least national support so resources and means are no problem - but it becomes a question of motive; why would they create such a weapon in the first place?
Donatello - our wild card option - certainly has the technical know how to create such a device. And from salvaging Shredder and Kraang lairs, its perfectly possible significant mutagen could be salvaged. However he would have no motive to make it into a weapon of any magnitude, far less one that size. Unless perhaps it was needed for some other crisis - after all the moon is shown to be massively damaged and a mutagen bomb on Earth would not have affected it. If the weapon had been created to deal with another threat and had malfunctioned in some way, the results could have been catastrophic. However RoboDon shows no remorse for any such mistake, something that seems highly unlikely of his character if such an event were his fault.
So reviewing the options it seems most likely that - barring an unknown threat - Baxter Stockman is the likeliest candidate for the disaster. With the EPF attempting to deal with another extra-terrestrial threat as a potential 2nd option.
While I have my theorizing hat on...
As for the device itself.... If it were as powerful as suggested, destroying the entire human race and leaving only mutants, there is no feasible way Leo could have survived being at the epicentre. The blastwave alone would have seen to him, and all the others.
I suspect its probably simpler to presume the device acted to blast mutagen into the upper atmosphere, where it would act like a massive dirty bomb, scattering tiny doses of weaponised mutagen across a huge area and allowing wind to naturally spread it. Its likely huge numbers of exposed people would have died shortly afterward from unstable mutation, with the fall out affecting crops, vegetation and natural wildlife across the USA. The Eastern US Coast and its massive cities would have been severely hit, with wind patterns carrying the mutagenic clouds west and south.
The resulting political fallout of the USA being completely crippled could well have then brought massive conflict outside the US, while inside the US citizenry is tearing itself apart coping with devastated infrastructure, millions mutated, and millions more wild and mutated.
The US evacuates what it can in a huge refugee crisis, further destabilizing everywhere else while it struggles with anti mutant sentiment. It would be most likely that it would be around this period that Casey, April, Karai and Shinigami would have met their ends. Aprils broken Tessen implies a death in combat, rather than from mutation for instance.
Its likely the US is declared a quarantine zone while the mutated fauna and flora wreak havoc. Given its only 50 yrs ahead and the skies are reasonably clear, it seems unlikely that the desertification we see is a result of nuclear war. So its possible Raph is actually incorrect in his assumption - and its only the North American continent that is a mutant wasteland. Which also explains why Oasis exists at all and seems to be extremely large - presumably they would have reached the edge of the affected area.
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