Detect ~500 uV change and output 3.3V?
I am not aware of such good comparators, but there are sigma-delta ADC on market that have crazy resolution. So you can use a differential preamplifier with reference 12.7mV and some gain, then a differential ADC and a microcontroller. 

But the question is so weird, that i would guess you do something wrong from the beginning. What is that device with it's output? Is it some kind of a sensor?