Energy-sensitive cryogenic detectors for high-mass biomolecule mass spectrometry

Energy-sensitive calorimetric detectors that operate at low temperatures ("cryogenic detectors") have recently been applied for the first time as ion detectors in time-of-flight mass spectrometry. Compared to conventional, ionization-based detectors, which rely on secondary electron formation or the charge created in a semiconductor, cryogenic detectors measure low-energy solid state excitations created by a particle impact. This energy sensitivity of cryogenic detectors results in several potential advantages for TOF-MS. Cryogenic detectors are expected to have near 100% efficiency even for very large, slow-moving molecules, in contrast to microchannel plates whose efficiency drops considerably at large mass. Thus, cryogenic detectors could contribute to extending the mass range accessible by TOF-MS and help improving detection limits. In addition, the energy resolution provided by cryogenic detectors can be used for charge discrimination and studies of ion fragmentation, ion-detector interaction, and internal energies of large molecular ions. Cryogenic detectors could therefore prove to be a valuable diagnostic tool in TOF-MS. Here, we give a general introduction to the cryogenic detector types most applicable to TOF-MS including those types already used in several TOF-MS experiments. We review and compare the results of these experiments, discuss practical aspects of operating cryogenic detectors in TOF-MS systems, and describe potential near future improvements of cryogenic detectors for applications in mass spectrometry.