Optical detection methods for mass spectrometry of macroions

Detection of macroions has been a challenge in the field of mass spectrometry. Conventional ionization-based detectors, relying on production and multiplication of secondary electrons, are restricted to detection for charged particles of m/z < 1 x 10(6). While both energy-sensitive and charge-sensitive detectors have been developed recently to overcome the limitation, they are not yet in common use. Photon-sensitive detectors are suggested to be an alternative, with which detection of macroions (or charged particles) by either elastic light scattering (ELS) or laser-induced fluorescence (LIF) has been possible. In this article, we provide a critical review on the developments of novel optical detection methods for mass spectrometry of macroions, including both micron-sized and nano-sized synthetic polymers as well as high-mass biomolecules. Design and development of new spectrometers making possible observations of the mass spectra of macroions with sizes in the range of 10-10(3) nm or masses in the range of 1-10(6) MDa are illustrated. The potential and promise of this optical approach toward macroion detection with high efficiency are discussed in practical aspects.