Resolving measurement of large (~ GDa) chemical/biomolecule complexes with multimode nanomechanical resonators

Mass sensing by nanomechanical resonators can be routinely performed for analytes of mass ranging from kDa to tens of MDa. Measurement of the heavier analytes (up to hundreds of GDa) that are relevant to viruses, and many biological and chemical complexes, still remains one of the main challenges to be solved. Some studies propose the heavy analyte identification by accounting for its mass, stiffness and binding effects. However, the necessity of using the sophisticated computational tools complicates their widespread use in the nanomechanical mass spectrometry. Here, we report on the heavy analyte mass spectrometry (~ GDa) using the multimode nanomechanical resonators, which is directly applicable to analytes of arbitrary mass, stiffness and dimensions. This identification, based on the simultaneous measurement of the multiple by analyte induced resonant frequency shifts, only requires the analyte to resonator mass ratio between 0.001 and 0.02. We show that the analyte stiffness and binding effects must be considered for the lower mass ratios (< 0.001), while for the higher mass ratios (> 0.02) the inaccuracies in determined mass are independent of both the analyte stiffness and binding effects, and increase with the mass of analyte. Validity of present results have been demonstrated by comparing predictions with the recent experimental measurements performed on the micro-/nanomechanical resonator-based mass spectrometers. Our findings, together with the provided software, which enables an easily accessible determination of the effects of analyte properties on the frequency response, present a novel paradigm in a design of the nanomechanical resonators for mass sensing in GDa range.