Nanoelectrospray ionization coupled to a linear charge detection array ion trap spectrometer for single viral particles analysis

TL;DR

This work addresses the challenge of analyzing intact viral particles by mass spectrometry, proposing a stand-alone CDMS instrument that combines nanoelectrospray ionization with a linear charge-detection array ion trap (ConeArrayTrap) to simultaneously measure time-of-flight (related to $m/z$) and ion charge for single particles. The authors detail a new eight-tube linear detector array, optimized via SIMION, and demonstrate two operational modes (transmission and trapping) to achieve high-throughput single-particle measurements. Validation with human adenovirus 5 and norovirus-like particles shows a representative mass of $154 ext{ MDa}$ and charge near 230 for hAdV5, with low noise in transmission mode and extended trapping times improving charge precision for single ions. The instrument is designed for stand-alone operation and integration into the ARIADNE-Vibe platform, with plans to couple it to Omnitrap for enhanced ion preparation and to deploy a high-performance DAQ system for simultaneous dual-channel data collection, enabling practical high-throughput viral metrology in environmental and biomedical contexts.

Abstract

This work presents the implementation of a new charge detection mass spectrometer (CDMS) design that operates in a stand-alone mode, thanks to its integration with nanoelectrospray ionization. More specifically, this innovative CDMS consists of a linear charge detection array ion trap spectrometer that combines an eight-tube detector array with conical electrodes. This configuration allows for recording data in both transmission mode (linear array) and ion trapping mode (ConeArrayTrap), which enables the measurement of time-of-flight (related to the mass-to-charge ratio) along with the charge of individual ions. As a result, this design supports high-throughput metrology of viruses at the single-particle level. The devices and geometry of the instrument have been developed based on ion optics simulations. The performance of the current instrument is demonstrated using human norovirus-like particles (hNoVLP) and Adenovirus Ad(5) (hAdV5).

Figures (8)

• Figure 1: a) General view of the apparatus. b) Example of signal traces (droplets) coming from the 2 sets of 4 CDDs clearly visible in the zoom-in panel c).
• Figure 2: Scheme of the constructed CDMS instrument used in this work. The DC experienced by the ions through their position in the CDMS are presented for the transmission mode and the two trapping modes (sharp and broad).
• Figure 3: a-c) Different cone geometries considered for the trapping mode. d) Acceptance of the selected cone a) according to ion beam divergence and axis offset. e) Illustration of simulated ion trajectory trapped (red) between the 2 cones.
• Figure 4: Simulated signal traces for the 3 ions in linear array (transmission) mode. The properties of the 3 ions can be found in Table \ref{['tab:IONsimion']} of appendix \ref{['app:SIMION']}. The top line corresponds to the traces out of the tubes and the bottom line corresponds to their derivatives.
• Figure 5: SIMION simulation of the trapping efficiency for the linear charge detection array ion trap spectrometer as a function of the reduced parameter $\varepsilon$. Points: Experimental trapping efficiency for oscillations of single hNoVLPs ions in the trap. A trapping efficiency of 100 represents 20 ms trapping time.