The state-of-the-art mass sensing so far has been rather developed along the resolution axis, reaching atomic-scale detection, than into the direction of high-speed. This paper reports a novel self-calibrating technique, making high-speed inertial mass sensors capable of instant high-resolution particle detection and weighing. The sensing nanoelectromechanical resonator is embedded into a phase-locked loop and the sensor-inherent nonlinear phase-frequency relation is exploited for auto-calibration. A tunable on-chip carbon nanotube based mass balance serves as a case study of small-size and low-cost environmental and healthcare applications. Tunability and a phase-locked loop topology make the system widely universal and invariant to nanotube characteristics. Operational for tube eigenfrequencies up to 385 MHz, the circuit integration in a 180 nm technology achieves instantaneous zeptogram resolution, while yoctogram precision is obtained within the tenth of a second. These figures of merit range at the physical limits of carbon nanotube resonators, in both mass- and time-resolution. (C) 2014 Elsevier Ltd. All rights reserved