Charge Detection Mass Spectrometry

  Charge detection mass spectrometry (CDMS) is an emerging field of mass spectrometry that offers an alternative to time of flight MS (TOF-MS) and FTICR-MS for measuring high mass ions. In those conventional types of mass spectrometry, the mass-to-charge ratio (m/z) is measured of packets of ions. For very large ions such as protein complexes and viruses, the m/z spectra can be poorly resolved, precluding a determination of the ions’ masses. CDMS directly measures the charge and the m/z of individual ions as they pass near an electrode and induce an image charge on the electrode. Multiplying the charge and m/z ratio together directly yields the masses of the ions, circumventing the problem of lack of resolution in the m/z spectrum.

Ion Flight Path Through Detection Cylinder and Corresponding Signal Output

  In more detail, we pass ions through a dual hemispherical deflection analyzer to select out ions of a particular kinetic energy. Those ions are transferred into an electrostatic ion trap, inside of which is a metal charge detector tube. As an ion oscillates back and forth through the charge detector, a periodic signal is induced on the charge detector. A Fourier transform is used to extract the characteristic frequency of the ion oscillating in the ion trap, from which we calculate the ion’s m/z. From the magnitude of the peak in the Fourier transform, we can calculate the ion’s charge. We multiply the charge and the m/z together for each individual ion to obtain a true mass spectrum.

  A reflectron time-of-flight mass spectrometer (TOF-MS) is also placed in tandem with the CDMS Ion Trap. With this in place, TOF-MS spectra can be generated under the same ion generation and entrance conditions, and the results can be compared and correlated with the CDMS Ion Trap spectra.

  With this technology, we have collected true mass spectra of hepatitis B virus capsid, revealing previously unknown conformers. These conformers would be extremely difficult to identify with conventional mass spectrometry.

 

Coupling With a Quadrupole Mass Filter

  A large m/z quadrupole mass filter is being developed to further improve the capabilities of the CDMS Ion Trap. Two signals are generated 180° out phase. The RF amplitude and DC offset of these waves can be adjusted to change the slope of the mass scan line across the stability region, affecting which masses are transmitted as well as the mass resolution. The frequency of the waves is scanned to transmit different ion masses. Since the voltage amplitude and offset are not scanned, it is much easier to keep the ratio of these two values constant while scanning. The large dynamic range of frequencies that can be scanned allow our quadrupole to theoretically pass much larger ions than traditional quadrupoles. We also avoid the large voltage amplitudes required by traditional quadrupoles in order to pass large ions.

  A new interface is also being developed to further enhance desolvation of large ions and to improve the mass resolution that can be obtained with our instrument.