Processing gain and noise in multi-electrode impedance cytometers: Comprehensive electrical design methodology and characterization

We introduce a novel technique for minimizing false positives and improving the fidelity of signals detected with impedance cytometry. We make use of interdigitated multi-finger electrodes for introducing redundancy and robustness in impedance based detection of micro- and nanoparticles. Multi-electrode impedance sensors provide multiple peaks and unique signatures for single cells and particles, and can be used in conjunction with match filters to provide processing gain. This approach is particularly useful in minimizing false positives, which is particularly difficult for signals with low signal-to-noise ratio. The unique signature provided by multi-electrode sensors results in higher signal-power compared to single electrode pair sensors, and can also result in more fidelity in distinguishing particles from noise. This technique holds the potential of using micro-scale channels for detection of nanoscale particles such as viruses and even individual proteins. Previous work has shown extraction of signal from noise using multi-electrode sensors. To the best of our knowledge, this manuscript presents the first comprehensive attempt to characterize processing gain improvement and system noise in multi-electrode sensors by directly comparing simultaneous measurements obtained from sensors fabricated along the same channel. By measuring simultaneously the electrode pairs along a single channel, consistency in flow rate and buffer conditions is ensured, while other experimental assay-to-assay variations are minimized. We achieve high SNR for particles as small as 1 um in a 30 μm wide by 10 diameter tall pore. SNR and noise measurements for different electrode configurations and excitation frequencies is thoroughly studied. The results of this study demonstrated that while increasing number of electrodes resulted in increased processing gain, noise levels also increased with larger number of electrode fingers, thus total SNR remained relatively unchanged. Our investigations showed that this increase in noise is likely due to electrochemical reactions at the surface of the electrode dominating the total noise.