A low-power, impedance-based integrated circuit (IC) readout architecture is presented for cell analysis and cytometry applications. A three-electrode layout and source-differential excitation cancels baseline current prior to the sensor front-end, which enables the use of a high-gain readout circuit for the difference current. A lock-in architecture is employed with down-conversion and up-conversion in the feedback loop, enabling high closed-loop gain (up to 10 M$\Omega$) and high bandwidth (up to 40 MHz). A hybrid-RC feedback network mitigates the SNR degradation seen over a wide operating frequency range when using purely capacitive feedback. The effect of phase shift on the closed-loop system gain and noise performance are analyzed in detail, along with optimization strategies, and the design includes fine-grained phase adjustment to minimize phase error. The impedance sensor was fabricated in a 0.18 $\mu$ m CMOS process and consumes 9.7 mW with an operating frequency from 50 kHz to 40 MHz and provides adjustable bandwidth. Measurements demonstrate that the impedance sensor achieves 6 pA $_\text{rms}$ input-referred noise over 200 Hz bandwidth at 0.5 MHz modulation frequency. Combined with a microfluidic flow cell, measured results using this source-differential measurement approach are presented using both monodisperse and polydisperse sample solutions and demonstrate single-cell resolution, detecting 3 $\mu$ m diameter particles in solution with 22 dB SNR.