A Kalman filter for estimating nanopore channel conductance in voltage-varying experiments

Time-varying voltage patterns have expanded the capabilities of the nanopore instrument for single molecule manipulation and measurement, in research and commercial applications. The ability to apply time-varying voltages enhances the nanopore as a tool for single-molecule biophysical studies, for example, by permitting dynamic force spectroscopy. A challenge with voltage-varying experiments is that capacitance in the system is excited and masks the contribution of the nanopore channel conductance in the measured current. The channel conductance, however, is the parameter that is used to infer the dynamics of the complex (e.g., DNA, or DNA-protein) in the pore, and also the parameter that can reveal the sequence of the DNA nucleotides as the DNA passes through the pore in nanopore sequencing. We present the first derivation and experimental implementation of a Kalman filter for estimating the channel conductance under time-varying voltage conditions. The estimator accurately recovers the step-change in open channel conductance that occurs when the voltage changes polarity, shown here in simulated and experimental conditions with sinusoidal voltages with varying amplitude and frequency. Future work will apply the estimator to detect smaller step changes induced by DNA-protein complexes on the nanopore, and by DNA nucleotides that pass through the nanopore.