Hadamard Transform Time-of-Flight Mass Spectrometry

A new mode of operation of a time-of-flight mass spectrometer (TOFMS) is described and demonstrated. A continuous ion beam emerging from the ion source is accelerated and then modulated by a pseudorandom sequence of “on” and “off” pulses. The data acquisition period is set to match the period of the modulation sequence, and data are acquired synchronously with the modulation of the ion beam. The modulation sequence is deconvoluted from the data using a fast Hadamard transform (FHT) algorithm to extract the time-of-flight distribution of the ions. This multiplexing scheme increases the ion usage to ∼50% for a single detector instrument and ∼100% for a multiple detector instrument, which improves the signal level considerably over that of conventional TOFMS. The gains in signal lead to an improved signal-to-noise ratio or alternatively reduced data acquisition time, giving HT-TOFMS a major instrumental advantage over conventional TOFMS in a number of applications at little additional cost. Positive mode electrospray ionization mass spectra of tetrabutylammonium perchlorate, cesium chloride, and a protein mixture of cytochrome c and ubiquitin are presented to illustrate the method and the device.