Concepts of single-particle mass analysis using mass photometry and charge-detection MS on an Orbitrap
(A) In MP, biomolecules’ masses are determined through their refractivity, whereby the light scattered by a biomolecule is proportional to its mass. Upon detection of ∼2,000 individual molecules (∼5 min acquisition time), statistical analysis of the cumulative distribution of particles enables mass determination, as shown in the top-right panel.
(B) In CDMS, an amplitude of the single ion signal induced on the Orbitrap electrodes is proportional to the charge of the ion. A few ion detection events are recorded per scan. After detecting ∼1e4-5 particles (∼10–60 min acquisition time), accurate masses are determined from populations of particles separated in z and m/z space. Statistical analysis of the cumulative distribution of particles enables mass determination, as shown in the top-right panel.