Multiple Ion Charge Extraction (MICE) for High-Throughput Charge Detection Mass Spectrometry.

Charge detection mass spectrometry (CD-MS) is a single-particle technique, where the masses of individual ions are determined from simultaneous measurements of their mass-to-charge ratio (m/z) and charge. The ions are trapped in an electrostatic linear ion trap (ELIT) and oscillate back and forth through a conducting cylinder connected to a charge-sensitive amplifier. The oscillating ions generate a periodic signal that is processed with fast Fourier transforms (FFTs) to obtain the oscillation frequency (which is related to m/z) and magnitude (which is proportional to the charge). The simultaneous trapping of two or more ions is a way to increase throughput. However, when multiple ions are trapped, it is possible that some of them have overlapping oscillation frequencies, which can lead to an error in the charge determination. To avoid this error, results from overlapping ions are usually discarded. When measurements are performed with many trapped ions, the most abundant m/z species are discarded at a higher rate, which affects the relative abundances in the mass distribution. Here, we report the development of a post-processing method called multiple ion charge extraction (MICE) that uses a statistical approach to assign charges to ions with overlapping frequencies. MICE recovers single-ion information from high signal measurements and makes the relative abundances more resilient to the signal intensity. This approach corrects for high signal m/z biasing, allowing analysis to be faster and more reliable. Using MICE, CD-MS measurements were made at rates of 120 ions/s with little m/z biasing.