A Perspective of Multi-Reflecting TOF MS.

Time-of-flight mass spectrometry (TOF MS) excels in rapid and high-sensitivity analysis, making it a cornerstone of analytical chemistry. But as sample complexity explodes in omics studies, so does the need for higher resolving power to ensure accurate results. Traditional TOF instruments face a challenge: achieving high resolution often requires a very large instrument. To overcome this limitation, scientists developed alternative designs for TOF analyzers called multi-pass TOF analyzers (MPT). These MPT analyzers come in two main configurations: multi-turn (MTT) and multi-reflecting (MRT). Drawing on the authors' extensive experience, this review describes two decades of MPT advancements. It highlights the critical development of optimized analyzer designs, tracing the evolution towards mirror-based MRT instruments, generally providing superior resolution and spatial acceptance compared to MTT. While the manuscript attempts to overview MTT advances, it primarily focuses on MRT technology. Additionally, the review explores the role of orthogonal accelerators and trap pulse converters, comparing their efficiency and the dynamic range limits imposed by space charge effects. By comparing various MRT configurations and commercially available instruments, the review sets out to inform and empower researchers so they can make informed decisions about MRT mass spectrometers.