ARTICLE pubs.acs.org/ac
Frequency-Scanning MALDI Linear Ion Trap Mass Spectrometer for Large Biomolecular Ion Detection I-Chung Lu,† Jung Lee Lin,† Szu-Hsueh Lai,†,‡ and Chung-Hsuan Chen*,†,‡,§ †
Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang District, Taipei 115, Taiwan Department of Chemistry & Chemical Biology, National Taiwan University, Taipei, Taiwan § Institute of Atomic & Molecular Sciences, Academia Sinica, Taipei, Taiwan ‡
ABSTRACT: This study presents the first report on the development of a matrixassisted laser desorption ionization (MALDI) linear ion trap mass spectrometer for large biomolecular ion detection by frequency scan. We designed, installed, and tested this radio frequency (RF) scan linear ion trap mass spectrometer and its associated electronics to dramatically extend the mass region to be detected. The RF circuit can be adjusted from 300 to 10 kHz with a set of operation amplifiers. To trap the ions produced by MALDI, a high pressure of helium buffer gas was employed to quench extra kinetic energy of the heavy ions produced by MALDI. The successful detection of the singly charged secretory immunoglobulin A ions indicates that the detectable mass-to-charge ratio (m/z) of this system can reach ∼385 000 or beyond.
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ecently, the linear ion trap (LIT) has attracted more and more attention since it can easily be combined with other mass analyzers such as Fourier transform ion cyclotron resonance and Orbitrap or operated as a stand-alone mass spectrometer. The most significant advantage of the LIT is its greater ion trapping capacity than that of a 3D ion trap.1 It can reduce the concern of the space charge effect compared to the same number of ions trapped in a 3D trap due to the larger volume of the LIT to trap ions. Compared with a 3D quadrupole ion trap, the LIT has demonstrated a significant improvement in proteomic analyses due to its higher trapping capacity and short duty cycle.1,2 In the future, proteomic and metabolomic analyses are expected to become critically important for the analysis of biomedical samples. Unfortunately, most commercially available LITs can only cover the region of small mass-to-charge ratio (m/z < 6000). Large biomolecules (>100 000 Da) usually cannot be directly detected with a high efficiency by the LIT. Therefore, the bottom-up analysis based on the analysis of small peptides produced by trypsin digestion and the help of protein ID through a library check has often been used for proteomic analysis. Mutated and post-translational proteins cannot be routinely analyzed since the top-down analysis has much lower detection sensitivity. To overcome this shortcoming, a powerful mass spectrometer that is able to detect a broad mass range with a high dynamic range is essential. The present voltage scanning LIT has been used for peptide analysis but has the limitation of a low mass-to-charge ratio (m/z < 6000). Accordingly, extending the detectable mass range of the LIT has a special advantage for top-down proteomic analysis. To increase the mass range with a low mass-to-charge ratio in an ion trap, electrospray ionization (ESI)3 to produce multiply charged ions is generally adopted. However, the production of multiply charged ions with ESI often leads to very complex spectra. The same type of molecules with r 2011 American Chemical Society
several different numbers of charges would spread the signals into many peaks and lower the sensitivity of detection. Therefore, the detection efficiency for very large biomolecules is always low even though ESI can produce multiply charged ions. Furthermore, the multiply charged ions might also increase the space charge effect inside ion traps. On the basis of the above considerations, ESI is not suitable for a sample containing a large number of different compounds. When ESI is used as an ionization source, the samples usually need preseparation by HPLC. On the contrary, singly charged ions produced by matrixassisted laser desorption ionization (MALDI)4 can significantly reduce these disadvantages. MALDI is very convenient for sample preparation and getting the entire mass profile of a complex sample. Nevertheless, the limitation of low m/z (100 000 Da) analysis. The approach of MALDI-LIT causes ions enriched at a single m/z. This feature makes the mass spectrum simpler, especially in large biomolecular ions. Future plans for this instrument will be focused on achieving better resolution and further increasing the detection efficiency at large m/z. Resonance ejection will also be employed in the frequency-sweeping process to improve the mass accuracy and resolution. In conclusion, this work demonstrates the development of a frequency scan MALDI-LIT mass spectrometer which can be expected to perform routine biomolecule analysis to cover a very broad mass range with a high sensitivity. It has the advantage to perform further collision-induced dissociation, which is not easy to achieve with a MALDI-TOF mass spectrometer.
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dx.doi.org/10.1021/ac202083c |Anal. Chem. 2011, 83, 8273–8277
