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The authors present a novel approach to perform the readout of a genetic sensor using a configurable architecture with extremely low drift with temperature and low sensitivity to the drift of mobile gate oxide charges. The proposed architecture, able to detect small changes of U.V. absorbance, calculates the analog weighted difference between the gate / source voltages of a floating gate and a reference nMOS transistor fabricated using a single poly technology. The theoretical dependence of the obtained results on both device and circuit parameters has carefully been analyzed. Experimental results show that the circuit offers a valid solution to decrease the error due to temperature variation during operation. Moreover, the measurement procedure is sufficiently quick for neglecting threshold voltage shifts due to mobile charges. Finally, the proposed approach has a particular advantage in integrated system design, since it is compatible with high-density MOS logic.