Fast impedance spectroscopy: General aspects and performance study for single ion channel measurements

In the present work, we propose a novel technical approach in time domain impedance spectroscopy enabling both enhanced time and current resolution by an improved data analysis and hardware setup. We introduce nonstationary time-to-frequency conversion methods such as short-time Fourier transform and wavelet transform resulting in an improved time resolution. The combination of a time domain impedance spectrometer with a patch-clamp amplifier enables the resolution of gigaohm impedance at low perturbation signal amplitudes. A fast impedance spectroscopy (FIS) setup is presented which is optimized for biophysical application of single ion channel measurements in supported biomembranes. The applicability and performance of the technique is first evaluated by simulations. It is then verified by measurements on model circuits which exhibit the characteristic key properties of single ion channel measurements. Here, FIS improves the time resolution by about three orders of magnitude down to milliseconds. The general aspects derived in this work are also valid in other fields, where the spectral information of a perturbation applied on a system and its response is analyzed, e.g., mechanical impedance spectroscopy and microrheology.