This Letter presents a fully integrated bio-system with the property of high sensitivity for electrochemical detection, which can intrinsically measure electrochemical characteristics with cyclic voltammetry. In normal circumstances, ultra-low electrolytes exist in tissue solution, which is difficult to accurately detect the oxidation/reduction signals, limited by the innate circuit and liquid noise. Hence, the conventional topology of the potentiostat circuit is improved and proposed in this Letter to remove the required analogue-to-digital converter (ADC). The overall operational mechanism of the potentiostat behaves like a single-slope ADC, which achieves a compact, easily implemented, and low-noise design. Additionally, the effective capacitance of potentiostat and liquid resistance make an RC integration to further suppress out-of-band noise, thereby enabling the low-electrolyte detection and improving detecting sensitivity. To simulate the low-electrolyte environment, only 0.01 M (M = mol/l) phosphate buffered saline background solution is used and required to demonstrate its feasibility of the concept. The measured results show the sensor chip with high sensitivity to sense resistive variation of electrochemical action in low electrolytes.