HADAMARD TRANSFORM TIME-OF-FLIGHT MASS SPECTROMETRY Matthew Robbins, Griffin Barbula, Richard Perry
Because time-of-flight mass spectrometry (TOFMS) involves a pulsed detection method, efficient detection of continuous ion sources remains a challenge. Increases in duty cycle (the fraction of ions that are detected) usually come at the expense of mass resolution and/or mass range. In an effort to decouple these figures of merit, our lab has developed a novel form of TOFMS that offers a 100% duty cycle over a wide mass range.1
Briefly, in this method ions entering the MS are rapidly switched between two detection states using a known sequence. Because the modulation sequence is based on Hadamard matrices, we have termed this method Hadamard transforms time-of-flight mass spectrometry (HT-TOFMS). Rapid modulation results in multiple ion packets that simultaneously move through the drift region and interpenetrate one another as they fly. In contrast, in a traditional TOFMS experiment a single ion packet moves through the drift region and is detected before a new packet is introduced. In HT-TOFMS, the acquired signal is the time-shifted superposition of all the packetsí mass spectra which can be decoded using knowledge of the applied modulation sequence. Because the modulation scheme allows us to detect more ions per unit time when compared to traditional, on-axis TOFMS, HT-TOF produces mass spectra with increased signal-to-noise properties, permits greater detection sensitivity, or enables faster spectral acquisition. Some areas of active research are:
New Ion Gating Devices and Ion Optics: In HT-TOFMS, Bradbury-Nielson gates are used for modulation of the ion beam. We continue to develop techniques for macro-4 and microfabrication5 of these devices and test their applicability for our method.
Imaging TOF: Because 100% duty cycle work requires a two anode detector, we have worked to expand our research using arbitrary position detection systems. We currently employ multichannel plate detectors with delay line anodes in acquisition of our HT-TOF data.
HT-TOFMS Kinetics: Because HT-TOF is a 50 or 100% duty cycle technique, more ions are collected within a given time window than with traditional TOFMS. This signal advantage can in turn be used to acquire more statistically significant spectra in a given time period. HT-TOFMS has the potential to push into the millisecond regime of kinetics where other modern MS is limited to seconds in full scan mode.
Coupling to Chromatographic and Electrophoretic Separations: The continuous nature and high spectral acquisition rate of HT-TOFMS make it an ideal detector for separation techniques, particularly those which produce time-narrow peaks.
DESI: Desorption electrospray ionization (DESI), an ambient pressure ionization technique, has shown promise for high sample throughput. By coupling DESI to HT-TOFMS, the sampling rate of DESI can be tested in a regime not accessible by other MS techniques with lower spectral acquisition rates.
O. Trapp, J.R. Kimmel, O.K. Yoon, I.A. Zuleta, F.M. Fernandez, and R.N. Zare, "Continuous two-channel time-of-flight mass spectrometric detection of electrosprayed ions," Angew. Chem. Int. Ed.43, 6541-6544 (2004).
J.R. Kimmel, O.K. Yoon, I.A. Zuleta, O.Trapp, and R.N. Zare, "Peak height precision in Hadamard Transform time-of-flight mass spectra," J. Am. Soc. Mass Spectrom.16, 1117-1130, (2005).
O. K. Yoon, I. A. Zuleta, J. R. Kimmel, M. D. Robbins, and R. N. Zare, "Duty Cycle and Modulation Efficiency of Two-Channel Hadamard Transform Time-of-Flight Mass Spectrometry," J. Am. Soc. Mass Spectrom.16, 1888-1901 (2005).
O.K. Yoon, I.A. Zuleta, M.D. Robbins, G.K. Barbula, and R.N. Zare, "Simple Template-Based Method to Produce Bradbury-Nielsen Gates," J. Am. Soc. Mass Spectrom.18, 1901-1908 (2007).
I. A. Zuleta, G. K. Barbula, M. D. Robbins, O. K. Yoon, and R. N. Zare, "Micromachined Bradbury-Nielsen Gates," Anal. Chem.79, 9160-9165 (2007).
M. D. Robbins, O. K. Yoon, I. A. Zuleta, G. K. Barbula, and R. N. Zare, "Computer-Controlled, Variable-Frequency Power Supply for Driving Multipole Ion Guides," Rev. Sci. Inst.79, 034702 (2008).
O. K. Yoon, M. D. Robbins, I. A. Zuleta, G. K. Barbula, and R. N. Zare, "Continuous Time-of-Flight Ion Imaging: Application to Fragmentation," Anal. Chem.80, 8299 (2008).