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. © 1999 John Wiley & Sons, Inc., Mass Spec Rev 18: 155–186, 1999