Atmospheric Pressure Mass Spectrometry of Single Viruses and Nanoparticles by Nanoelectromechanical Systems

Abstract

Mass spectrometry of intact nanoparticles and viruses can serve as a potent characterization tool for material science and biophysics. Inaccessible by widespread commercial techniques, the mass of single nanoparticles and viruses (>10MDa) can be readily measured by nanoelectromechanical systems (NEMS)-based mass spectrometry, where charged and isolated analyte particles are generated by electrospray ionization (ESI) in air and transported onto the NEMS resonator for capture and detection. However, the applicability of NEMS as a practical solution is hindered by their miniscule surface area, which results in poor limit-of-detection and low capture efficiency values. Another hindrance is the necessity to house the NEMS inside complex vacuum systems, which is required in part to focus analytes toward the miniscule detection surface of the NEMS. Here, we overcome both limitations by integrating an ion lens onto the NEMS chip. The ion lens is composed of a polymer layer, which charges up by receiving part of the ions incoming from the ESI tip and consequently starts to focus the analytes toward an open window aligned with the active area of the NEMS electrostatically. With this integrated system, we have detected the mass of gold and polystyrene nanoparticles under ambient conditions and with two orders-of-magnitude improvement in capture efficiency compared to the state-of-the-art. We then applied this technology to obtain the mass spectrum of SARS-CoV-2 and BoHV-1 virions. With the increase in analytical throughput, the simplicity of the overall setup, and the operation capability under ambient conditions, the technique demonstrates that NEMS mass spectrometry can be deployed for mass detection of engineered nanoparticles and biological samples efficiently.

Apodization Specific Fitting for Improved Resolution, Charge Measurement, and Data Analysis Speed in Charge Detection Mass Spectrometry

“…Single ion mass measurements have been demonstrated with a number of different types of mass spectrometers, including Fourier transform ion cyclotron resonance, , quadrupole ion trap, − Orbitrap, , and charge detection mass spectrometers that employ simple electrostatic traps. − In each of these methods, the frequency of ion motion is related to ion m / z . The charge can be determined either by stripping or adding a single charge, ,, or it can be determined directly from the amplitude of the signal on charge-sensitive detectors. ,,− Single ion detection has also been demonstrated with time-of-flight mass spectrometry with energy-sensitive superconducting tunnel junction cryodetectors and with nanomechanical resonators. , …”

“…18,23,26−29 Single ion detection has also been demonstrated with time-offlight mass spectrometry with energy-sensitive superconducting tunnel junction cryodetectors 30 and with nanomechanical resonators. 31,32 In charge detection mass spectrometry (CDMS) with electrostatic ion traps, the signal amplitude and hence charge of an ion can be determined more accurately by increasing measurement time to improve signal-to-noise (S/N) ratios. This improved accuracy comes at a cost of analysis time.…”

Exploring Masses and Internal Mass Distributions of Single Carboxysomes in Free Solution Using Fluorescence and Interferometric Scattering in an Anti-Brownian Trap

“…A number of approaches have been developed to determine the mass of single tiny objects. Mechanical oscillator and cantilever-based , methods have been developed for directly weighing individual nanoparticles. Measuring mass and structural information about proteinaceous assemblies has also been achieved with scanning transmission electron microscopy (STEM) and cryo-electron tomography (cryo-ET) more recently .…”

Exploring masses and internal mass distributions of single carboxysomes in free solution using fluorescence and interferometric scattering in an anti-Brownian trap

“…A number of approaches have been developed to determine the mass of single tiny objects. Mechanical oscillator 9 and cantilever-based 10 , 11 methods have been developed for directly weighing individual nanoparticles. Measuring mass and structural information about proteinaceous assemblies has also been achieved with scanning transmission electron microscopy (STEM) 12 and cryo-Electron Tomography (cryo-ET) more recently.…”