How to Generate a Calibration Signal?
Sure, you can just use a CMOS logic chip (gate, buffer whatever) and follow it up by a voltage divider. Say your circuit runs at 5V, you could use a 100K resistor and a 10 ohm resistor. That will give you a 500uV p-p square wave that goes from 0 to 500uV. If you need to offset it by -250uV that can be done in a few different ways. One way is to connect a fixed resistor from the 10 ohm resistor of 200K and connect it to -5V. 

You could use the micro directly, but using a separate buffer allows you to use a reference at the same voltage as the supply and control the currents a bit better to get a really clean square wave. 







simulate this circuit &ndash; Schematic created using CircuitLab

Obviously you need to be very careful where the ground goes for the 10 ohm resistor- not to some noisy digital ground but to a nice quiet analog ground. 

You can easily get an unadjusted accuracy of 0.1% or 0.2% with common cheap parts. The output impedance will be 10 ohms, which I imagine will not pose a problem for you.