Dynamic Calibration Enables High-Accuracy Charge Measurements on Individual Ions for Charge Detection Mass Spectrometry.

Charge detection mass spectrometry (CDMS) depends on the measurement of the charge induced on a cylinder by individual ions by means of a charge-sensitive amplifier. For high-accuracy charge measurements, the detection cylinder is embedded in an electrostatic linear ion trap (ELIT), and the ions oscillate back and forth through the cylinder so that multiple measurements are made. To assign the charge state with a low error rate, the charge of each ion must be determined with an uncertainty (root-mean-square deviation) of around 0.2 elementary charges. We show here that high-accuracy charge measurements can be achieved for large ions by dynamic calibration of the charge measurement using an internal standard. The internal standard is generated by irradiating the detection cylinder, by means of a small antenna, with a radiofrequency signal. Using this approach, we have obtained a relative charge uncertainty of around 5 × 10, allowing charge-state resolution to be achieved for single ions with up to 500 charges. In another application of this approach, the detection cylinder is irradiated with a signal that counteracts the transients generated when the potentials on the ELIT end-caps are switched to trapping mode. Using this approach, the dead time after switching (during which the signal cannot be analyzed) has been reduced by more than an order of magnitude. With charge-state resolution for ions with up to 500 charges, we were able to calibrate the charges precisely. The results show that the response of the charge-sensitive amplifier with dynamic calibration is linear to within a small fraction of an elementary charge.