Improving Signal to Noise Ratios in Ion Mobility Spectrometry and Structures for Lossless Ion Manipulations (SLIM) using a High Dynamic Range Analog-to-Digital Converter.

Signal digitization is a commonly overlooked part of ion mobility-mass spectrometry (IMS-MS) workflows, yet it greatly affects signal-to-noise ratio and MS resolution measurements. Here, we report on the integration of a 2 GS/s, 14-bit ADC with structures for lossless ion manipulations (SLIM-IMS-MS) and compare the performance to a commonly used 8-bit ADC. The 14-bit ADC provided a reduction in the digitized noise by a factor of ∼6, owing largely to the use of smaller bit sizes. The low baseline allowed threshold voltage levels to be set very close to the MCP baseline voltage, allowing for as much signal to be acquired as possible without overloading or excessive digitization of MCP baseline noise. Analyses of Agilent tuning mixture ions and a mixture of heavy labeled phosphopeptides showed that the 14-bit ADC provided a ∼1.5-2× signal-to-noise (S/N) increase for high intensity ions, such as the Agilent tuning mixture ions and the 2+ and 3+ charge states of many phosphopeptide constituents. However, signal enhancements were as much as 10-fold for low intensity ions, and the 14-bit ADC enabled discernible signal intensities otherwise lost using an 8-bit digitizer. Additionally, the 14-bit ADC required ∼14-fold fewer mass spectra to be averaged to produce a mass spectrum with a similar S/N as the 8-bit ADC, demonstrating ∼10× higher measurement throughput. The high resolution, low baseline, and fast speed of the new 14-bit ADC enables high performance digitization of MS, IMS-MS, and SLIM-IMS-MS spectra and provides a much better picture of analyte profiles in complex mixtures.