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This paper focuses on a differential voltage measurement in low-voltage automotive devices whose subunits are separated with a low-side safety switch. In contrast to conventional applications with high-side switches, a common-mode voltage (CMV) with negative polarity exists at the input of the signal conditioning circuitry. To overcome the shortage of dedicated integrated circuits capable of withstanding negative CMV, the paper investigates single- and two-stage differential circuits with single-supplied operational amplifiers to find a cost-optimized counterpart. In addition, the proposed procedure tunes the circuit parameters in such a manner to obtain the largest possible full-scale range at the output. Though, such optimization results in very uncommon values for gain and reference voltages. This issue is additionally evaluated for reference voltages that are either cost-effective or more easily accessible to increase the circuit feasibility. Since the impact of resistances on circuits' behaviour could be diminished to a great extent using high-precision and matched pair resistors, the sensitivity analysis was investigated only for a reference voltage change. Furthermore, a reversed termination of measured voltages results in a simplified reference voltage selection without hindering circuits' performance, proven by simulation and experimental results. [ABSTRACT FROM AUTHOR]