New Prospero: A Boosted Detector to Expand the MALDI-ToF Mass Spectrometry Range Beyond m/z 50,000

Macromolecules, such as proteins, large fragments of DNA, viruses, and bacteria, have gained significant interest in recent years due to their roles in biochemistry, medicine, and biopharmaceuticals. This increased interest necessitates the characterization and determination of their molecular mass, which can range from a few dozen kDa to several MDa.   Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) is a soft ionization technique that enables the detection of intact molecules. It consists of three main components: the ionization chamber, the analyzer where ions are separated according to their mass-to-charge ratio (m/z), and the detector. Theoretically, the mass range of MALDI-MS is unlimited, allowing for the detection of macromolecules. However, detector saturation and low ion velocity can significantly decrease the signal for higher masses.   In recent years, new detectors have been developed to overcome these challenges and facilitate the detection of larger molecules. One commonly used mass spectrometer detector is the microchannel plate (MCP), which releases electrons upon ion impact, triggering a chain reaction that creates an electron cloud for detection. At low velocities, the probability of initiating this chain reaction is reduced, thereby affecting the signal quality. The “new Prospero” detector addresses this issue by incorporating a booster before the MCP to increase ion velocity, thus enhancing the detection of larger molecules.   This talk will focus on the MALDI technique, its operation, advantages, and limitations. We will then present the new detector and explore how it addresses the mass limitation challenge by enhancing the signal of several proteins by up to 20 times compared to the conventional MCP.