Publications by authors named "Francisco A Fernandez-Lima"

13 Publications

  • Page 1 of 1

LESA Cyclic Ion Mobility Mass Spectrometry of Intact Proteins from Thin Tissue Sections.

Anal Chem 2020 05 27;92(9):6321-6326. Epub 2020 Apr 27.

Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, United States.

Liquid extraction surface analysis (LESA) is an ambient surface sampling technique that allows the analysis of intact proteins directly from tissue samples via mass spectrometry. Integration of ion mobility separation to LESA mass spectrometry workflows has shown significant improvements in the signal-to-noise ratios of the resulting protein mass spectra and hence the number of proteins detected. Here, we report the use of a quadrupole-cyclic ion mobility-time-of-flight mass spectrometer (Q-cIM-ToF) for the analysis of proteins from mouse brain and rat kidney tissues sampled via LESA. Among other features, the instrument allows multiple pass cyclic ion mobility separation, with concomitant increase in resolving power. Single-pass experiments enabled the detection of 30 proteins from mouse brain tissue, rising to 44 when quadrupole isolation was employed. In the absence of ion mobility separation, 21 proteins were detected in rat kidney tissue including the abundant α- and β-globin chains from hemoglobin. Single-pass cyclic ion mobility mass spectrometry enabled the detection of 60 additional proteins. Multipass experiments of a narrow / range (/ 870-920) resulted in the detection of 24 proteins (one pass), 37 proteins (two passes) and 54 proteins (three passes), thus demonstrating the benefits of improved mobility resolving power.
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http://dx.doi.org/10.1021/acs.analchem.9b05169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304663PMC
May 2020

Analysis of Chemotherapeutic Drug Delivery at the Single Cell Level Using 3D-MSI-TOF-SIMS.

J Am Soc Mass Spectrom 2016 12 31;27(12):2033-2040. Epub 2016 Aug 31.

Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA.

In this work, we show the advantages of label-free, tridimensional mass spectrometry imaging using dual beam analysis (25 keV Bi) and depth profiling (20 keV with a distribution centered at Ar) coupled to time of flight secondary ion mass spectrometry (3D-MSI-TOF-SIMS) for the study of A-172 human glioblastoma cell line treated with B-cell lymphoma 2 (Bcl-2) inhibitor ABT-737. The high spatial (~250 nm) and high mass resolution (m/Δm ~10,000) of TOF-SIMS permitted the localization and identification of the intact, unlabeled drug molecular ion (m/z 811.26 CHClNOS [M - H]) as well as characteristic fragment ions. We propose a novel approach based on the inspection of the drug secondary ion yield, which showed a good correlation with the drug concentration during cell treatment at therapeutic dosages (0-200 μM with 4 h incubation). Chemical maps using endogenous molecular markers showed that the ABT-737 is mainly localized in subsurface regions and absent in the nucleus. A semiquantitative workflow is proposed to account for the biological cell diversity based on the spatial distribution of endogenous molecular markers (e.g., nuclei and cytoplasm) and secondary ion confirmation based on the ratio of drug-specific fragments to molecular ion as a function of the therapeutic dosage. Graphical Abstract ᅟ.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088064PMC
http://dx.doi.org/10.1007/s13361-016-1485-yDOI Listing
December 2016

Secondary ion mass spectrometry imaging of Dictyostelium discoideum aggregation streams.

PLoS One 2014 9;9(6):e99319. Epub 2014 Jun 9.

Department of Chemistry and Biochemistry, Florida International University, Miami, Florida, United States of America.

High resolution imaging mass spectrometry could become a valuable tool for cell and developmental biology, but both, high spatial and mass spectral resolution are needed to enable this. In this report, we employed Bi3 bombardment time-of-flight (Bi3 ToF-SIMS) and C60 bombardment Fourier transform ion cyclotron resonance secondary ion mass spectrometry (C60 FTICR-SIMS) to image Dictyostelium discoideum aggregation streams. Nearly 300 lipid species were identified from the aggregation streams. High resolution mass spectrometry imaging (FTICR-SIMS) enabled the generation of multiple molecular ion maps at the nominal mass level and provided good coverage for fatty acyls, prenol lipids, and sterol lipids. The comparison of Bi3 ToF-SIMS and C60 FTICR-SIMS suggested that while the first provides fast, high spatial resolution molecular ion images, the chemical complexity of biological samples warrants the use of high resolution analyzers for accurate ion identification.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099319PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049834PMC
October 2015

Bi-Directional Ion Emission from Massive Gold Cluster Impacts on Nanometric Carbon Foils.

J Phys Chem C Nanomater Interfaces 2012 Apr 12;116(14):8138-8144. Epub 2012 Mar 12.

Department of Chemistry, Texas A&M University, College Station, Texas 77943-3144.

Carbon cluster emission from thin carbon foils (5-40 nm) impacted by individual Au(n) (+q) cluster projectiles (95-125 qkeV, n/q = 3-200) reveals features regarding the energy deposition, projectile range, and projectile fate in matter as a function of the projectile characteristics. For the first time, the secondary ion emission from thin foils has been monitored simultaneously in both forward and backward emission directions. The projectile range and depth of emission were examined as a function of projectile size, energy, and target thickness. A key finding is that the massive cluster impact develops very differently from that of a small polyatomic projectile. The range of the 125 qkeV Au(100q) (+q) (q ≈ 4) projectile is estimated to be 20 nm (well beyond the range of an equal velocity Au(+)) and projectile disintegration occurs at the exit of even a 5 nm thick foil.
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http://dx.doi.org/10.1021/jp212126mDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413922PMC
April 2012

Alkali Halide Nanotubes: Structure and Stability.

J Phys Chem C Nanomater Interfaces 2012 Mar;116(8)

Chemistry Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Accurate density functional theory (DFT) and coupled-cluster (CCSD) calculations on a series of (LiF) neutral clusters suggest that nanotube structures with hexagonal and octagonal transversal cross sections show stability equal to or greater than that of the typical cubic form of large LiF crystals. The nanotube stability was further corroborated by quantum dynamic calculations at room temperature. The fact that stable nanotube structures were also found for other alkali halides (e.g., NaCl and KBr) suggests that this geometry may be widely implemented in material sciences.
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http://dx.doi.org/10.1021/jp208090jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873780PMC
March 2012

Analysis of Fluorescent Proteins with a Nanoparticle Probe.

J Phys Chem Lett 2012 Feb;3(3):337-341

Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255.

This letter presents the first application of high energy, single nanoparticle probes (e.g., 520 keV Au(400) 2nm NP) in the characterization of surfaces containing fluorescent proteins (e.g., GFP variants) by their co-emitted photon, electron and secondary ion signals. NP induced protein luminescence increases with the NP incident energy, is originated by the NP impact and is transferred to the protein fluorophor via electronic energy transfer. Multi-electron emission is observed per single NP impacts and their distributions are specific to the target morphology and composition. Fragment ions of protein sub-units consisting of 2-7 amino acid peptides are observed under individual NP impacts that can be correlated to the random protein orientation relative to the impact site (e.g., outer layer or "skin" of the protein).
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http://dx.doi.org/10.1021/jz201547xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270945PMC
February 2012

Analysis of native biological surfaces using a 100 kV massive gold cluster source.

Anal Chem 2011 Nov 18;83(22):8448-53. Epub 2011 Oct 18.

Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255, United States.

In the present work, the advantages of a new, 100 kV platform equipped with a massive gold cluster source for the analysis of native biological surfaces are shown. Inspection of the molecular ion emission as a function of projectile size demonstrates a secondary ion yield increase of ~100× for 520 keV Au(400)(4+) as compared to 130 keV Au(3)(1+) and 43 keV C(60). In particular, yields of tens of percent of molecular ions per projectile impact for the most abundant components can be observed with the 520 keV Au(400)(4+) probe. A comparison between 520 keV Au(400)(4+) time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) data showed a similar pattern and similar relative intensities of lipid components across a rat brain sagittal section. The abundant secondary ion yield of analyte-specific ions makes 520 keV Au(400)(4+) projectiles an attractive probe for submicrometer molecular mapping of native surfaces.
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http://dx.doi.org/10.1021/ac201481rDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236644PMC
November 2011

A Study of Ion-Neutral Collision Cross Section Values for Low Charge States of Peptides, Proteins, and Peptide/Protein Complexes.

Int J Mass Spectrom 2010 Dec;298(1-3):111-118

Department of Chemistry, Texas A&M University, College Station, Texas, 77843, USA.

Here, we report ion-helium collision cross sections (CCS) for a number of peptide, small protein, and peptide/protein ionic complexes. The CCS values reported here are compared to previously reported results.[1, 2] We also compare values for low charge state species, i.e., [M + H](+) and [M + 2H](2+), formed by MALDI with values for high charge state species formed by ESI, and the measured CCSs are compared with predicted CCS for solid-state and solution phase structures and calculated structures obtained by using a protein-protein structure algorithm generator, based on a combined Biomolecular complex Generation with Global Evaluation and Ranking[3] and Multi Dimensional Scaling[4].
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http://dx.doi.org/10.1016/j.ijms.2009.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077763PMC
December 2010

Amino acid influence on copper binding to peptides: cysteine versus arginine.

J Am Soc Mass Spectrom 2010 Apr 11;21(4):522-33. Epub 2010 Jan 11.

Department of Chemistry, Texas A and M University, College Station, Texas 77843, USA.

Matrix assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) and theoretical calculations [density functional theory (DFT)] were utilized to investigate the influence of cysteine side chain on Cu(+) binding to peptides and how Cu(+) ions competitively interact with cysteine (-SH/SO(3)H) versus arginine. Results from theoretical and experimental (fragmentation reactions) studies on [M + Cu](+) and [M + 2Cu - H](+) ions suggest that cysteine side chains (-SH) and cysteic acid (-SO(3)H) are important Cu(+) ligands. For example, we show that Cu(+) ions are competitively coordinated to the -SH or SO(3)H groups; however, we also present evidence that the proton of the SH/SO(3)H group is mobile and can be transferred to the arginine guanidine group. For [M + 2Cu - H](+) ions, deprotonation of the -SH/SO(3)H group is energetically more favorable than that of the carboxyl group, and the resulting thiolate/sulfonate group plays an important role in the coordination structure of [M + 2Cu - H](+) ions, as well as the fragmentation patterns.
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http://dx.doi.org/10.1016/j.jasms.2009.12.020DOI Listing
April 2010

Petroleum crude oil characterization by IMS-MS and FTICR MS.

Anal Chem 2009 Dec;81(24):9941-7

Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.

Here, complementary ion mobility/mass spectrometry (IM/MS) and ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS analyses of light, medium, and heavy petroleum crude oils yielded distributions of the heteroatom-containing hydrocarbons, as well as multiple conformational classes. The IM/MS technique provides unique fingerprints for fast identification of signature conformational/compositional patterns, whereas FTICR MS analysis provides comprehensive heteroatom class distributions. IM/MS and FTICR MS results reveal an increase in compositional complexity in proceeding from light to medium to heavy crude oils. Inspection of the mobility results shows a high structural diversity for the C(n)H(h)XY (XY = N(1), S(1), N(1), O(1), NS, SO(1-2), NO(1-2), etc.) series, as well as a shift from planar to more compact three-dimensional structures with increasing mass.
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http://dx.doi.org/10.1021/ac901594fDOI Listing
December 2009

A new copper containing MALDI matrix that yields high abundances of [peptide + Cu]+ ions.

J Am Soc Mass Spectrom 2009 Jul 25;20(7):1263-71. Epub 2009 Feb 25.

Department of Chemistry, Texas A and M University, College Station, Texas 77843, USA.

The dinuclear copper complex (alpha-cyano-4-hydroxycinnamic acid (CHCA) copper salt (CHCA)(4)Cu(2)), synthesized by reacting CHCA with copper oxide (CuO), yields increased abundances of [M + xCu - (x-1)H](+) (x = 1-6) ions when used as a matrix for matrix-assisted laser desorption ionization (355 nm Nd:YAG laser). The yield of [M + xCu - (x-1)H](+) (x = 1 to approximately 6) ion is much greater than that obtained by mixing peptides with copper salts or directly depositing peptides onto oxidized copper surfaces. The increased ion yields for [M + xCu - (x-1)H](+) facilitate studies of biologically important copper binding peptides. For example, using this matrix we have investigated site-specific copper binding of several peptides using fragmentation chemistry of [M + Cu](+) and [M + 2Cu - H](+) ions. The fragmentation studies reveal interesting insight on Cu binding preferences for basic amino acids. Most notable is the fact that the binding of a single Cu(+) ion and two Cu(+) ions are quite different, and these differences are explained in terms of intramolecular interactions of the peptide-Cu ionic complex.
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http://dx.doi.org/10.1016/j.jasms.2009.02.025DOI Listing
July 2009

A novel approach to collision-induced dissociation (CID) for ion mobility-mass spectrometry experiments.

J Am Soc Mass Spectrom 2009 Jun 9;20(6):907-14. Epub 2008 Dec 9.

The Laboratory for Biological Mass Spectrometry, Department of Chemistry, Texas A and M University, College Station, Texas 77843-3255, USA.

Collision induced dissociation (CID) combined with matrix assisted laser desorption ionization-ion mobility-mass spectrometry (MALDI-IM-MS) is described. In this approach, peptide ions are separated on the basis of mobility in a 15 cm drift cell. Following mobility separation, the ions exit the drift cell and enter a 5 cm vacuum interface with a high field region (up to 1000 V/cm) to undergo collisional activation. Ion transmission and ion kinetic energies in the interface are theoretically evaluated accounting for the pressure gradient, interface dimensions, and electric fields. Using this CID technique, we have successfully fragmented and sequenced a number of model peptide ions as well as peptide ions obtained by a tryptic digest. This instrument configuration allows for the simultaneous determination of peptide mass, peptide-ion sequence, and collision-cross section of MALDI-generated ions, providing information critical to the identification of unknown components in complex proteomic samples.
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http://dx.doi.org/10.1016/j.jasms.2008.11.026DOI Listing
June 2009

Ion mobility-mass spectrometer interface for collisional activation of mobility separated ions.

Anal Chem 2009 Jan;81(2):618-24

Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.

An ion mobility-mass spectrometer (IM-MS) interface is described that can be employed to perform collisional activation and/or collision-induced dissociation (CID) with good transmission of mobility separated ions to the MS analyzer. The IM-MS interface consists of a stacked-ring ion guide design, where the field strength and pressure ratio can be operated such that structural rearrangement reactions and/or CID are achieved as a function of the effective ion temperature. The ion dynamics and collisional activation processes in the IM-MS interface are described as a function of the ion-neutral collisions, ion kinetic energies, and effective ion temperature. The applicability of the IM-CID-MS methodology to studies of peptide ion fragmentation is illustrated using a series of model peptides.
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http://dx.doi.org/10.1021/ac801919nDOI Listing
January 2009