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This paper describes progress toward an active tissue-contrast sensing microsystem that can be embedded at the tip of a fine biopsy needle. An analog CMOS chip is integrated with a piezoelectric sensor to reduce the impact of parasitic capacitances and allow differential sensing that will permit deep tissue sampling. The sensor element and the CMOS circuit are fabricated in-house and integrated onto the tip of a 20-gauge needle. The sensor module with integrated interface circuit has a size of 950 μm (L) × 350 μm (W) × 220 μm (H). It can successfully generate an oscillating signal as the readout of the integrated piezoelectric quartz sensor. Preliminary functional verification for sensing is provided by saline solutions of 0.5-3% concentration, representing a progressive increase of acoustic impedance. As expected the measured frequency shifts increase with higher saline concentration, indicating the validity of the sensor interface circuit design.