“…More recently, another approach has been emerging based on single-molecule field-effect transistors (smFETs), in which an individual molecule is immobilized on a nanoscale electrical circuit, such as a carbon nanotube (6)(7)(8)(9)(10)(11)(12) or silicon nanowire (13)(14)(15)(16). By recording fluctuations in the electrical conductance of such circuits, studies have reported the realtime monitoring of transitions between different conformational states, such as hybridization (17)(18)(19)(20), folding events in nucleic acids (17,21), enzymatic catalysis with a ultra-high sensitivity and specificity (22,23), and also other applications in biology and medicine, such as imaging (24,25) and drug delivery (26,27) to cancer and brain. Detecting and modeling the kinetics and thermodynamics of such molecular interactions from smFET recordings require robust data analysis tools that can handle challenging signal specificities: 1) the stochastic nature of the biomolecular system, 2) the possible non-stationarity of the molecular dynamics of the reaction system, such as changes between transient and steady-state conformations, 3) the multi-source composition of the sensor response, aggregating all the contributions from the biochemical system with those of the measurement medium and the sensor components into a single output, 4) the mixed noises (AWGN, flicker, and impulse) characteristic of FET devices, 5) the sensor baseline drift that can occur during long acquisitions, and 6) the sizable amount of data generated by such recordings, all together resulting in complex time series to idealize into a state trajectory.…”