Our current and future research is focused on the development of new generation instrumentation and methodologies for biomedical and behavioral research. In particular, our group is interested in the characterization of the chemical environment at the single cell and sub-cellular level of model cell systems and tissue sections using a "molecular microscope".


There are two main challenges in the molecular characterization of native surfaces: the quantity of sample available for analysis and the dynamic mass range. The long-term goal of our work is to develop nanometer probes for mass spectrometry based imaging for the study at the single cell and sub-cellular level of "native state" biological surfaces with: i) enhanced lateral resolution, ii) enhanced emission of molecular ions and iii) fast gas-phase, post-ionization separation techniques.


This integrated approach involves the instrument development and optimization of sample-friendly conditions for the generation of the molecular ions of interest, the design and generation of MS imaging calibration procedures and standards, the incorporation of high-throughput post-ionization separation and fragmentation techniques, the analysis of the gas-phase conformational space of molecular ions, and the characterization of the chemical environment at the single cell and sub-cellular level of model biological systems.



Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space


The ability to correlate experimental ion mobility data with candidate structures from theoretical modeling provides a powerful analytical and structural tool for the characterization of biomolecules. In the present paper, a theoretical workflow is described to generate and assign candidate structures for experimental trapped ion mobility and H/D exchange (HDX-TIMS-MS) data following molecular dynamics simulations and statistical filtering. The applicability of the theoretical predictor is illustrated for a peptide and protein example with multiple conformations and kinetic intermediates. The described methodology yields a low computational cost and a simple workflow by incorporating statistical filtering and molecular dynamics simulations. The workflow can be adapted to different IMS scenarios and CCS calculators for a more accurate description of the IMS experimental conditions. For the case of the HDX-TIMS-MS experiments, molecular dynamics in the “TIMS box” accounts for a better sampling of the molecular intermediates and local energy minima.







Towards unsupervised polyaromatic hydrocarbons structural assignment from



With the advent of high resolution ion mobility analyzers and their coupling to ultrahigh resolution mass spectrometers, there is a need to further develop a theoretical workflow capable of correlating experimental accurate mass and mobility measurements with tridimensional candidate structures. In the present work, a general workflow is de scribed for unsupervised tridimensional structural assignment based on accurate mass measurements, mobility measurements, in silico 2D-3D structure generation, and theoretical mobility calculations. In particular, the potential of this workflow will be shown for the analysis of polyaromatic hydrocarbons from Coal Tar SRM 1597a using selected accumulation - trapped ion mobility spectrometry (SA-TIMS) coupled to Fourier transform- ion cyclotron resonance mass spectrometry (FT-ICR MS). The proposed workflow can be adapted to different IMS scenarios, can utilize different collisional cross-section calculators and has the potential to include MSn and IMSn measurements for faster and more accurate tridimensional structural assignment.