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Analog to digital signal conditioning

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If I have a 12 bit ADC with a reference voltage of 4.096V it should be able to detect changes in voltage up to 1mV correct?

However when you attenuate a signal that is much larger than Vref, you are not going to get nice 1mv steps. What are the considerations one should make to help mitigate the differences to acheive the greatest accuracy/precision.

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