Broadband single cell impedance spectroscopy using maximum length sequences: theoretical analysis and practical considerations

Measurements of the dielectric (or impedance) properties of cells can be used as a general characterization and diagnostic tool. In this paper, we describe a novel impedance spectroscopy technique for the analysis of single biological cells in suspension. The technique uses maximum length sequences (MLS) for periodic excitation signal in a microfluidic impedance cytometer. The method allows multi-frequency single cell impedance measurements to be made in a short time period (ms). Spectral information is obtained in the frequency domain by applying a fast M-sequence transform (FMT) and fast Fourier transform (FFT) to the time domain response. Theoretically, the impedance is determined from the transfer function of the system when the MLS is a current excitation. The order of the MLS and sampling rate of A/D conversion are two factors that determine the bandwidth and spectral accuracy of the technique. Experimentally, the applicability of the technique is demonstrated by characterizing the impedance spectrum of red blood cells (RBCs) in a microfluidic cytometer. The impedance is measured within 1 ms at 512 discrete frequencies, evenly distributed in the range from 976.56 Hz to 500 kHz. The measured spectrum shows good agreement with simulations.