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In this paper, we report on the noise analysis of low current measurement systems for biomedical applications and their fundamental limits. We analyzed resistive feedback, capacitive feedback and current amplifier circuits for low current measurement systems. Detailed noise analysis for different biomedical applications are presented and matched with measurement data using a 0.5-μm fabrication process. Based on the theoretical analysis and the corresponding measurement results, the capacitive feedback system provides better noise performance for the measurement of low current than the others. The capacitive feedback circuit is capable of measuring 750 fA RMS at a 10 kHz sampling rate, whereas the resistive feedback provides 4 pA and the current conveyor provides 600 pA at the same bandwidth. This paper provides design guidelines to maximize the performance of low current measuring system for biomedical instrumentation and to provide the best performance available with CMOS technologies.