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In this paper, integration of liquid crystal (LC) capacitive chemical and biological sensor with the CMOS interface circuit has been investigated. The LC microchip provides better sensitivity compared to discrete interfacing and array of sensors can be fabricated to reduce false positives. For high sensitivity detection, the excitation signal voltage and frequency have been examined and sensor capacitance plots are provided. Two on-chip interdigitated capacitors provide differential sensor measurement to cancel common environmental parasitic effects. The LC sensor interface circuit includes a low noise charge amplifier, synchronous demodulator, low pass filter and a sigma-delta A/D converter. The preamplifier noise has been minimized using a nonlinear optimization algorithm. The preamplifier has 15 aF resolution with 1 kHz bandwidth, while the microchip has 14-bit resolution using AMI 0.5 μm technology.