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I am using Reaper with the guitar plugged directly into my interface (Scarlet 2-i2), and I get a decent sound with the TSE 808 -> TSE x50 -> Poulin LeCab -> ReEq. However, I have a high noise threhold when cranking the gain for the sound that i want, to the point where it interferes with my regular signal (even with a noise gate). Would it potentially reduce the noise floor if I were to use one or more USB opto-isolators, or would I be better off getting a device with paired transformers to break the electrical chain and reduce noise/ground loops?

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You don't have a ground loop as there is no connection between the guitar and the computer chassis (other than via the interface).

You can try using a DI box - this might improve your situation but without having access to the setup it is hard to diagnose correctly.

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If the noise is induced in the pickups - eg from your monitor screen or fluorescent lighting, then no amount of electrical isolation will cure it.

The only cure is switching off the offending sources, or moving away from them.
A long-shot 3rd option is to get an old Line6 Variax, which doesn't use magnetic pickups at all & is therefore induced-voltage-free.

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    Yes, there is some noise induced from the monitor scren. Oh well.
    – Math1000
    Commented Dec 31, 2019 at 1:17

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