Lab-on-a-chip systems have been attracting a growing attention for the perspective of miniaturization and portability of bio-chemical assays. Here we present a the design and characterization of a miniaturized, USB-powered, self-contained, 2-channel instrument for impedance sensing, suitable for label-free tracking and real-time detection of cells flowing in microfluidic channels. This original circuit features a signal generator based on a direct digital synthesizer, a transimpedance amplifier, an integrated square-wave lock-in coupled to a Σ▵ ADC converter, and a digital processing platform. Real-time automatic peak detection on two channels is implemented in a FPGA. System functionality has been tested with an electronic resistance modulator to simulate 1% impedance variation produced by cells, reaching a time resolution of 50μs (enabling a count rate of 2000 events/s) with an applied voltage as low as 200mV. Biological experiments have been carried out counting yeast cells. Statistical analysis of events is in agreement with the expected amplitude and time distributions. 2-channel yeast counting has been performed with concomitant dielectrophoretic cell separation, showing that this novel and ultra compact sensing system, thanks to the selectivity of the lock-in detector, is compatible with other AC electrical fields applied to the device.© (2011) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.