Optimization of multi-frequency techniques used for cell membrane capacitance estimation

Measurements of cell membrane capacitance serve as an indicator of cell membrane surface area and thus have traditionally been used in stimulus-secretion coupling to monitor exocytosis and endocytosis of secretory vesicles. In order to accurately monitor secretion, high-resolution methods of tracking small (10^-15 F) changes in baseline capacitance must be utilized. Most presently used techniques require assumptions that are not appropriate under all recording conditions or suffer from a low signal-to-noise ratio (SNR). This paper proposes to improve upon current estimation techniques by developing an optimized multi-frequency sinusoidal stimulus waveform for accurate capacitance estimations. The waveform is designed by jointly optimizing the phase and voltage of individual frequency components so as to minimize the theoretical bound on the variance of the capacitance estimate, while maintaining a preselected limit on the overall stimulus magnitude.