Biological Impedance Spectroscopy: Lock-In Amplifier

Impedance spectroscopy is a method for analyzing biological cells and is used in other bio-impedance applications such as electrical impedance tomography (EIT). A key advantage is that no additional preparation or conditioning of the biological cells is necessary, in contrast to many optical analysis methods. Through miniaturization of the measurement setup the necessary amount of analyte can also be greatly reduced, which is another important benefit.

The figure below shows how the impedance changes, when a cell passes the electrodes in the microchannel. Two electrodes are placed at the ceiling and two at the bottom of the channel. The electrodes at the ceiling are then excited with a sinusoidal voltage, and the current is measured differentially at the bottom electrodes. An impedance change results, which is shown below the channel schematic and is entitled "Cell signal".

A lock-in amplifier has been used to perform the impedance measurements. Since it can measure both, amplitude and phase deviation of the input signal, it is an optimal choice for impedance spectroscopy measurements of cells. The figure below explains the functional principle of a lock-in amplifier.

The sensor is supplied with a periodic signal, called local oscillator (L.O), that modulates the sensor signal with a defined frequency. This modulated signal is then amplified, optionally filtered, and then demodulated with the same L.O. This allows for filtering out unwanted disturbances and noise (e.g. drift and 1/f noise) of all frequencies other than the modulation frequency. The lock-in amplifier can be realized in CMOS-technology, which will enable miniaturization and a further integration of the whole measurement system.

Publications

• T. Lanz, S. Hafizovic, J. Rothe, R. Streichan, N. Goedecke, F. Heer A. Hierlemann, “Differential Impedance Spectrometer and Vision System for the Analysis of Single Cells,” Proceedings of the 15th International Conference on Solid-State Sensors, Actuators & Microsystems, Transducers, Denver, CO, USA, June 21-25, 2009, 1297-1300, ISBN 978-1-4244-4193-8.

Contact

Dr. Flavio Heer, see also our spinoff company Zurich Instruments