The ability to perform structure analysis of a molecule,such as the conformations of a protein,is critically important to understand its functions at a molecular level.Conventionally,tandem mass spectrometry(MS)has been used to probe the structure of an ion.More recently,ion mobility spectroscopy(IMS)and H/D exchange have also been with MS to provide complementary ion structure information.Due to the complexity and dynamic nature of molecular structures,especially for biomolecules,there has been increasing demand for new and complementary ion structure analysis technologies in the MS area.In this study,the method of obtaining biomolecule collision cross sections(CCS)in Fourier transform(FT)based mass analyzers was discussed.By developing new ion-neutral collision models within modern high-resolution FT based mass analyzers(including FT-ICR and quadrupole ion trap),[1,2] CCSs of biomolecules could be extracted from the linewidth of FT-mass spectra.Experimental results from FT-ICR MS show that the measured CCSs of peptides and proteins with this method have a linear relationship with those from IMS measurements.[3,4] Theoretical and simulation results show that a close to 200 resolving power could be achieved in ion CCS measurements by integrating advanced time-frequency theory in instrument design and data analyses processes.[5,6] By providing complementary ion structure information,this method could be used together with tandem mass spectrometry and ion mobility spectroscopy techniques.Although many questions and challenges remain,this technique potentially would greatly enhance the ion structure analysis capability of a mass spectrometer,and provide a new tool for chemists and biochemists.