CMOS impedance biosensor array with active tone cancellation for simultaneous impedance and nonlinearity measurement

We present a 6×6 array of impedance biosensor circuits implemented in 0.18 μm CMOS. Each pixel contains impedance-measuring circuitry plus tone cancellation circuitry to enable simultaneous measurement of the impedance´s dependence on DC bias point. Changes in both impedance and nonlinearity of the electrode-solution interface can indicate binding of the biomolecule of interest. Our measurement scheme uses a large-amplitude low-frequency tone superimposed on the traditional small-signal excitation. The weakly nonlinear nature of the electrode-solution interface generates intermodulation tones which can be used to quantify the amount of nonlinearity. To avoid the large-amplitude signal saturating the amplifier output, a digital feedback loop actively cancels the low-frequency component by injecting an antiphase current at the summing node of the transimpedance amplifier, so that only the small-signal tone and intermodulation tones remain. Impedance changes of 0.2% can be detected. Each measurement pixel occupies 0.14 mm² and consumes 1.9 mW.