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This application relates to the field of microfluidic biosensing technology, and discloses a data acquisition and control system based on organ-on-a-chip microfluidics. The system includes a rhythm-locked loop module, a phase-controlled acquisition module, an impedance detection module, a data compensation module, and a closed-loop control module. The system generates a phase-locked clock by analyzing the pulse rhythm of the microfluidic pump drive current and chamber pressure timing data and aligning it with time-domain phase-locking. During the steady-state window of the laminar flow, it performs phase-controlled synchronous acquisition of the sensor array to obtain the raw biochemical dataset. During the low-level interval of the clock, it performs electrochemical impedance spectroscopy to obtain a fouling compensation factor. Based on this factor, it compensates and calibrates the data of each modality to obtain a biological phenotypic feature matrix, which is then input into a model predictive controller to achieve adaptive microfluidic closed-loop control. This application effectively improves the signal-to-noise ratio of data acquisition and the robustness of microenvironment control during long-term operation of organ-on-a-chip systems.