Hi Jonathan,
If you apply different Vref to the LMP91000, the main impact is in the working point of the TIA (its internal Zero).
Consider that the min Vref you can apply is 1.5V, while the max is the Vdd you have connected to the LMP91000. In order to minimize the effect of the change of Vref, I suggest to work at 67% of VREF when you work at low VREf values and then decrese it to 50% and then 20% when you work at high Vref values. In this way you minimize the variation of the Internal zero. The common mode of the TIA will be almost stable.
When you set the internal zero, you set refernce point (0ppm level), but its precision depends on the precision of VREF and precision of the voltage divider which generates the 20%, 50% and 67% of the VREF. Anyway making a single ended measurement (VOUT vs. GND) you usually subtract the value of the internal zero in order to have a voltage which is proportional to the current sunk/source bu the sensor. To be more precise yuo should remove also the offset between RE and WE intorduced by the TIA.
Moreover consider that when yuo change the bias voltage (when you program the % of VREF) you have different offset between Reference and Working electrode. In order to eliminate this offset I suggest to put the ADC between C1 and C2 pin. In this way you have a differential measurement.
regards,
Domenico