Electron capture dissociation (ECD) was first reported in 1998 by Zubarev, Kelleher, and McLafferty.¹  ECD produces odd-electron ions by the recombination of a low-energy electron (<1 eV) with a multiply charged precursor cation.^2,3  Electron capture by a singly charged precursor results in a neutral product that is invisible to the mass spectrometer. The electron energy range can be increased (3–13 eV) to implement hot electron capture dissociation (HECD) which produces secondary ion fragments not found in conventional ECD, including some useful side chain cleavages that can distinguish isomeric or isobaric residues, for example leucine and isoleucine.⁴  This experiment is performed in positive ion mode. This is a non-ergodic process and therefore produces extensive fragmentation of peptide backbones while maintaining labile post-translational modifications (PTMs).³  ECD is an ideal tool for determining structural details for positively charged analytes such as proteins and some oligosaccharides. Until recently, ECD was considered an instrument-specific technique mostly utilized in Fourier transform ion cyclotron resonance (FTICR) mass spectrometers. The capability of ECD to efficiently fragment peptides and proteins, and to identify PTMs by both top-down and bottom-up approaches has created great interest in this activation method. Recent innovations provide the means to implement ECD in other widely used mass spectrometers. ECD has been implemented in ion-trap mass spectrometers by applying an external magnetic field, or by pulsing electrons into the ion trap during a node in the radio-frequency (RF) amplitude.^5,6  In recent years atmospheric pressure electron capture dissociation (AP-ECD) has gained popularity due to its ability to be applied to virtually any electrospray ionization (ESI) source. The success of AP-ECD has been demonstrated on a quadrupole/time-of-flight MS.⁷  In 2009, an electromagnetostatic ECD cell was developed, and implemented on a triple quadrupole MS.⁸  Since then the electromagnetostatic ECD cell has been implemented on a variety of mass spectrometers.^9,10  This cell utilizes a high density of electrons to provide high fragmentation efficiency in a short timescale (microseconds), and has been integrated into beam instruments such as time-of-flight, triple quadrupoles, and Orbitrap hybrid mass spectrometers.¹¹  For Orbitrap MS instruments, the cell is mounted on the front end of the higher-energy collisional dissociation (HCD) cell connecting to the exit lens of the C-trap, as shown in Figure 6.1. Ubiquitin and myoglobin were investigated, and both yielded a higher sequence coverage (80% and 60% respectively) than CID alone and yielded a significantly higher percentage of assigned fragments (69% and 74% respectively). This data shows the ability to successfully implement ECD on mass spectrometry platforms other than an FTICR MS.