Christophe Masselon

• PhD
• Principal Investigator at Atomic Energy and Alternative Energies Commission, Grenoble, France

Single particle mass analysis methods allow the measurement and characterization of individual nanoparticles, viral particles, as well as biomolecules like protein aggregates and complexes. Several key benefits are associated with the ability to analyze individual particles rather than bulk samples, such as high sensitivity and low detection limits...

Nanoelectromechanical systems (NEMS)‐based mass spectrometry (MS) is an emerging technique that enables determination of the mass of individual adsorbed particles by driving nanomechanical devices at resonance and monitoring the real‐time changes in their resonance frequencies induced by each single molecule adsorption event. We incorporate NEMS in...

Nanoelectromechanical systems (NEMS)‐based mass spectrometry (MS) is an emerging technique that enables determination of the mass of individual adsorbed particles by driving nanomechanical devices at resonance and monitoring the real‐time changes in their resonance frequencies induced by each single molecule adsorption event. We incorporate NEMS in...

Nanoelectromechanical resonators (NEMS) have recently emerged as mass measurement devices with interesting potential, and with mass ranges hardly covered by conventional techniques, they offer the possibility of studying intact nanoparticles, whether artificial or biological. However, different physical phenomena perturb the NEMS signals, lowering...

Progress in genome sequencing technologies has transfigured biological research, including the field of virology. This had the unintended consequence of relegating structural phenotypic evaluations of viruses, and the associated methods, to mere complements of genomic approaches. Building on the work of Mazzone, and in light of recent advances in s...

Mass measurements in the mega-to giga-Dalton range are essential for the characterization of natural and synthetic nanoparticles, but very challenging to perform using conventional mass spectrometers. Nano-electro-mechanical system (NEMS) based MS has demonstrated unique capabilities for the analysis of ultra-high mass analytes. Yet, system designs...

Due to their unique size-dependent properties, nanoparticles (NPs) have many industrial and biomedical applications. Although NPs are generally characterized based on the size or morphological analysis, the mass of whole particles can be of interest as it represents the total amount of material in the particle regardless of shape, density, or eleme...

Due to their physical properties, nanomechanical sensors (NEMS) can achieve mass measurements in the mega- to gigadalton range, which is hardly obtained with conventional mass-spectrometers. However, NEMS signals are subject to noise, causing a loss of mass resolution and thus emphasizing the need of noise control. We propose a denoising model that...

When studying viruses, the most prevalent aspects that come to mind are their structural and functional features, but this leaves in the shadows a quite universal characteristic: their mass. Even if approximations can be derived from size and density measurements, the multi MDa to GDa mass range, featuring a majority of viruses, has so far remained...

Nanomechanical mass spectrometry has proven to be well suited for the analysis of high mass species such as viruses. Still, the use of one-dimensional devices such as vibrating beams forces a trade-off between analysis time and mass resolution. Complex readout schemes are also required to simultaneously monitor multiple resonance modes, which degra...

It has been demonstrated in the recent years that nanomechanical mass spectrometry was well suited for the analysis of specific high mass species such as viruses. Still, the exclusive use of one-dimensional devices such as vibrating beams forces a trade-off between analysis time (related to capture area) and mass resolution (inversely proportional...

In discovery proteomics experiments, tandem mass spectrometry and data-dependent acquisition (DDA) are classically used to identify and quantify peptides and proteins through database searching. This strategy suffers from known limitations such as under-sampling and lack of reproducibility of precursor ion selection in complex proteomics samples, l...

Bridging the mass gap Viruses and many large biomolecule complexes are in a mass range that is challenging to measure with conventional mass spectrometry methods. Nanomechanical resonators can determine masses of impacting molecules, but separation methods often lose too much of the sample to be efficient. Dominguez-Medina et al. used an aerodynami...

One of the main challenges to overcome to perform nanomechanical Mass Spectrometry (NEMS-MS) analysis in a practical time frame stems from the size mismatch between the analyte beam and the extremely small nanomechanical detector area. We report here the demonstration of NEMS-MS with arrays of 20 individually addressed nanomechanical resonators whe...

Most technologies, including conventional mass spectrometry, struggle to measure the mass of particles in the MDa to GDa range. Although this mass range appears optimal for nanomechanical resonators, early nanomechanical-MS systems suffered from prohibitive sample loss, extended analysis time or inadequate resolution. Here, we report on a novel sys...

Correction for 'Predictive chromatography of peptides and proteins as a complementary tool for proteomics' by Irina A. Tarasova et al., Analyst, 2016, 141, 4816-4832.

On the applicability of peptide retention time prediction software for data acquired using different LC conditions.

Urothelial bladder cancer is a condition associated with high recurrence and substantial morbidity and mortality. Non-invasive urinary tests that would detect bladder cancer and tumor recurrence are required to significantly improve patient care. Over the last decade, numerous bladder cancer candidate biomarkers have been identified in the context...

Proteomics aims to achieve complete profiling of the protein content and protein modifications in cells, tissues and biofluids, and to quantitatively determine changes in their abundances. This information serves to elucidate cellular processes and signal-ing pathways, and to identify candidate protein biomarkers and/or therapeutic targets. Analyse...

Advances in high-throughput proteomics have led to a rapid increase in the number, size, and complexity of the associated data sets. Managing and extracting reliable information from such large series of data sets require the use of dedicated software organized in a consistent pipeline to reduce, validate, exploit, and ultimately export data. The c...

In the last couple of decades, considerable effort has been focused on developing methods for quantitative and qualitative proteome characterization. The method of choice in this characterization is mass spectrometry used in combination with sample separation. One of the most widely used separation techniques at the front end of a mass spectrometer...

An inexpensive digital microfluidic (DMF) chip was fabricated by screen-printing electrodes on a sheet of polyimide. This device was manually integrated with surface acoustic wave nebulization (SAWN) MS to conduct hydrogen/deuterium exchange (HDX) of peptides. The HDX experiment was performed by DMF mixing of one aqueous droplet of angiotensin II w...

Urine has garnered tremendous interest over the past decade as a potential source of protein biomarkers for various pathologies. However, due to its low protein concentration and the presence of interfering compounds, urine constitutes a challenging analyte in proteomics. In the context of a project aimed at the discovery and evaluation of new cand...

One of the most important early developments in the field of proteomics was the advent of automated data acquisition routines that allowed high-throughput unattended data acquisition during HPLC introduction of peptide mixtures to a tandem mass spectrometer. Prior to this, data acquisition was orders of magnitude less efficient being based entirely...

Current approaches to Mass Spectrometry (MS) necessarily rely on the ionization of the analytes of interest and subsequent spectrum interpretation is based on the mass-to-charge ratios of the ions. The resulting charge state distribution can be very complex for high-mass species which may hinder correct interpretation. A new form of MS analysis bas...

Cells react to cues from their environment using various mechanisms that include changes in metabolites, gene expression, protein binding partners, protein localization, and protein posttranslational modifications (PTMs), all of which contribute to altered cellular signatures that enable appropriate cellular responses. Given the seemingly infinite...

Normal biological tissues harbour different populations of cells with intricate spacial distribution patterns resulting in heterogeneity of their overall cellular composition. Laser microdissection involving direct viewing and expertise by a pathologist, enables access to defined cell populations or specific region on any type of tissue sample, thu...

Inversion of the order of peptide elution in reversed-phase liquid chromatography under changing separation conditions, such as gradient slope has been considered. Using a six-protein proteolytic peptide standard and available literature data, the occurrence frequency and importance of this phenomenon in proteomic studies utilizing methods of shotg...

Surface acoustic wave nebulization (SAWN) is a novel method to transfer nonvolatile analytes directly from the aqueous phase to the gas phase for mass spectrometric analysis. The lower ion energetics of SAWN and its planar nature make it appealing for analytically challenging lipid samples. This challenge is a result of their amphipathic nature, la...

Surface acoustic wave nebulization (SAWN) has recently been reported as a novel method to transfer non-volatile analytes directly from solution to the gas phase for mass spectrometric analysis. Here we present a comparison of the survival yield of SAWN versus electrospray ionization (ESI) produced ions. A series of substituted benzylpyridinium (BzP...

To study chloroplast metabolism and functions, subplastidial localization is a prerequisite to achieve protein functional characterization. As the accurate localization of many chloroplast proteins often remains hypothetical, we set up a proteomics strategy in order to assign the accurate subplastidial localization. A comprehensive study of Arabido...

The cellular slime mold Dictyostelium discoideum is a soil-living eukaryote, which feeds on microorganisms engulfed by phagocytosis. Axenic laboratory strains have been produced that are able to use liquid growth medium internalized by macropinocytosis as the source of food. To better define the macropinocytosis process, we established the inventor...

Enterotoxin A (SEA) is a staphylococcal virulence factor which is suspected to worsen septic shock prognosis. However, the presence of SEA in the blood of sepsis patients has never been demonstrated. We have developed a mass spectrometry-based assay for the targeted and absolute quantification of SEA in serum. To enhance sensitivity and specificity...

This article was originally published in Proteomics 2011, 11 , 1160–1171, DOI 10.1002/pmic.201000566

Urine is an easily accessible bodily fluid particularly suited for the routine clinical analysis of disease biomarkers. Actually, the urinary proteome is more diverse than anticipated a decade ago. Hence, significant analytical and practical issues of urine proteomics such as sample collection and preparation have emerged, in particular for large-s...

Surface acoustic waves (SAW) can be generated along the surface of a piezoelectric material and efficiently transferred into fluid deposited on the surface to induce its nebulization. Recently, we demonstrated that surface acoustic wave nebulization (SAWN) can produce ions that are readily detectable by mass spectrometry (MS). Here we present the d...

Obtaining accurate protein profiles from homogeneous cell populations in heterogeneous tissues can enhance the capability to discover protein biomarkers. In this context, methodologies to access specific cellular populations and analyze their proteome with exquisite sensitivity have to be selected. We report here the results of an investigation usi...

Recent advances in the proteomics field have allowed a series of high throughput experiments to be conducted on chloroplast samples, and the data are available in several public databases. However, the accurate localization of many chloroplast proteins often remains hypothetical. This is especially true for envelope proteins. We went a step further...

Urine proteomics is emerging as a powerful tool for biomarker discovery. The purpose of this study is the development of a well-characterized "real life" sample that can be used as reference standard in urine clinical proteomics studies. We report on the generation of male and female urine samples that are extensively characterized by different pla...

Recent advances in the proteomic field have allowed high throughput experiments to be conducted on chloroplast samples and the data are available in several databases such as the Plant Protein Database (PPDB), or the SubCellular Proteomic Database (SUBA). However, the accurate localization of many proteins that were identified in different subplast...

Normal tissues are composed of different types of cells leading to complex heterogeneous areas. Under the control of a pathologist, laser microdissection is a powerful tool for procuring near-pure populations of targeted cell types from spécifie microscopic regions, or even from a single cell of interest of any tissue sections. This technique, whos...

Generation of a complex proteome database requires use of powerful analytical methods capable of following rapid changes in the proteome due to changing physiological and pathological states of the organism under study. One of the promising technologies with this regard is the use of so-called Accurate Mass and Time (AMT) tag peptide databases. Gen...

Recent advances in the proteomic field have allowed high-throughput experiments to be conducted on chloroplast samples. Many proteomic investigations have focused on either whole chloroplast or sub-plastidial fractions. To date, the Plant Protein Database (PPDB, Sun et al., 2009) presents the most exhaustive chloroplast proteome available online. H...

The IRMa toolbox provides an interactive application to assist in the validation of Mascot search results. It allows automatic filtering of Mascot identification results as well as manual confirmation or rejection of individual PSM (a match between a fragmentation mass spectrum and a peptide). Dynamic grouping and coherence of information are maint...

To comply with current proteomics guidelines, it is often necessary to analyze the same peptide samples several times. Between analyses, the sample must be stored in such a way as to conserve its intrinsic properties, without losing either peptides or signal intensity. This article describes two studies designed to define the optimal storage condit...

The development of mass spectrometry (MS)-based methodologies for high-throughput protein identification has generated a concomitant need for protein quantification. Numerous MS-based relative quantification methodologies have been dedicated to the extensive comparison of multiple proteomes. On the other hand, absolute quantification methodologies,...

The combination of liquid chromatography (LC) with mass spectrometry (MS) has become a mainstream proteome analysis strategy. In LC-MS, measured masses possess their "universal" scale derived from atomic mass tables. In contrast, the observed LC retention times (RT) are not tied to a conventional time scale, and depend on experimental conditions. H...

We report a premier side-by-side comparison of two leading types of monolithic nano-LC column (silica-C(18), polystyrene) in shotgun proteomics experiments. Besides comparing the columns in terms of the number of peptides from a real-life sample (Arabidopsis thaliana chloroplast) that they identified, we compared the monoliths in terms of peak capa...

Diverse mass spectrometric instruments have been used to provide data for accurate mass and retention time (AMT) tag proteomics analyses, including ion trap, quadrupole time-of-flight, and Fourier transform mass spectrometry (FTMS). An important attribute of these instruments, beside mass accuracy, is their spectral resolution. In fact, the ability...

Biology is transitioning from a largely qualitative, mostly descriptive science to a quantitative and ultimately predictive science. Advances in high throughput DNA sequencing have made increasing numbers of genome sequences available and enabled a âsystems❠level analysis of complex biological organisms. The ability to quantitatively measure the...

It is expected that the composition of the serum proteome can provide valuable information about the state of the human body in health and disease and that this information can be extracted via quantitative proteomic measurements. Suitable proteomic techniques need to be sensitive, reproducible, and robust to detect potential biomarkers below the l...

In proteomics, effective methods are needed for identifying the relatively limited subset of proteins displaying significant changes in abundance between two samples. One way to accomplish this task is to target for identification by MS/MS only the "interesting" proteins based on the abundance ratio of isotopically labeled pairs of peptides. We hav...

Ion transfer and storage using inhomogeneous radio frequency (RF) electric fields in combination with gas-assisted ion cooling and focusing constitutes one of the basic techniques in mass spectrometry today. The RF motion of ions in the bath gas environment involves a large number of ion-neutral collisions that leads to the internal activation of i...

An accurate mass and time (AMT) tag approach for proteomic analyses has been developed over the past several years to facilitate comprehensive high-throughput proteomic measurements. An AMT tag database for an organism, tissue, or cell line is established by initially performing standard shotgun proteomic analysis and, most importantly, by validati...

DNA damage can take the form of chemical lesions that interfere with DNA polymerization and therefore, the replication of DNA within a cell. In this report we examine the effect of a particular type of base modification, a 6-O-methyl group on a guanine base. Previous reports using different DNA polymerases have identified an induced base substituti...

An experimental approach for increasing the efficiency of Electron Capture Dissociation (ECD) with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is presented. The approach is based on manipulating the spatial distribution of an ion cloud inside an FTICR trap during electron irradiation, which is realized by using both on-re...

Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is playing an increasing role in the characterization of cellular systems owing to its capabilities for providing higher confidence of identification, increased dynamic range and sensitivity unmatched by other MS platforms. Particularly in proteomics, where global and quantitati...

A new collision-induced dissociation (CID) technique based on broadband tailored noise waveform (TNW) excitation of ions stored in a linear ion trap has been developed. In comparison with the conventional sustained off-resonance irradiation (SORI) CID method commonly used in Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), th...

Efforts to develop a liquid chromatography (LC)/mass spectrometry (MS) technology for ultra-sensitive proteomics studies (i.e., nanoscale proteomics) are described. The approach combines high-efficiency nanoscale LC (separation peak capacity of approximately 10(3); 15-microm-i.d. packed capillaries with flow rates of 20 nL min(-1), the optimal sepa...

Ultrasensitive nanoscale proteomics approaches for characterizing proteins from complex proteomic samples of <50 ng of total mass are described. Protein identifications from 0.5 pg of whole proteome extracts were enabled by ultrahigh sensitivity (<75 zmol for individual proteins) achieved using high-efficiency (peak capacities of approximately 10(3...

This work focuses on the development of a multidimensional electrokinetic-based separation/concentration platform coupled with electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) for achieving the high resolution and ultrasensitive analysis of complex protein/peptide mixtures. A microdialysis junction...

The ability to manipulate and effectively utilize small proteomic samples is important for analyses using liquid chromatography (LC) in combination with mass spectrometry (MS) and becomes more challenging for very low flow rates due to extra column volume effects on separation quality. Here we report on the use of commercial switching valves (150-m...

Multiplexed tandem mass spectrometry (MS/MS) has recently been demonstrated as a means to increase the throughput of peptide identification in liquid chromatography (LC) MS/MS experiments. In this approach, a set of parent species is dissociated simultaneously and measured in a single spectrum (in the same manner that a single parent ion is convent...

The aim of strategy for proteome analysis is to exploit a combination of instrumental and methodological approaches to provide broad proteome coverage, high sensitivity, and the capability for greatly increased throughput compared with conventional technologies. The chapter reviews the technological basis and progress toward a global proteomics str...

In the era of systems biology, computational and high-throughput experimental biological approaches are increasingly being combined to provide global snapshots of entire genomes and proteomes under tissue- and disease-specific conditions. The aim is to identify proteins changing in concentration and/or post-translational state and/or location, and...

A primary challenge in proteome measurements is to be able to detect, identify, and quantify the extremely complex mixtures of proteins. The relative abundances of interest span at least six orders of magnitude for mammalian proteomes, and this constitutes an intractable challenge for high throughput proteome studies. We have recently described a n...

Understanding biological systems and the roles of their constituents is facilitated by the ability to make quantitative, sensitive, and comprehensive measurements of how their proteome changes, e.g., in response to environmental perturbations. To this end, we have developed a high-throughput methodology to characterize an organism's dynamic proteom...

We have obtained relationships for frequency shifts resulting from the interference of spectral components for the magnitude mode Fourier transform. The approximation of a weak perturbation of well resolved peaks has been used. Both the low- and high-pressure limits for Fourier-transform ion cyclotron resonance (FTICR) operation have been considere...

An increasing number of proteomic strategies rely on liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect and identify constituent peptides of enzymatically digested proteins obtained from various organisms and cell types. However, sample preparation methods for isolating membrane proteins typically involve the use of detergents and...

Data-dependent external m/z selection and accumulation of ions is demonstrated in use with ESI-FTICR instrumentation, with two different methods for ion selection being explored. One method uses RF/DC quadrupole filtering and is described in use with an 11.5 tesla (T) FTICR instrument, while the second method employs RF-only resonance dipolar excit...

We describe and review progress towards a global strategy that aims to extend the sensitivity, dynamic range, comprehensiveness, and throughput of proteomic measurements for microbial systems based upon the use of polypeptide accurate mass tags (AMTs) produced by global protein enzymatic digestions. The two-stage strategy exploits high accuracy mas...

One of the key qualities of mass spectrometric measurements for biomolecules is the mass measurement accuracy (MMA) obtained. FTICR presently provides the highest MMA over a broad m/z range. However, due to space charge effects, the achievable MMA crucially depends on the number of ions trapped in the ICR cell for a measurement. Thus, beyond some p...

The mathematical and physical frequency shifts in fourier transform ion cyclotron (FTICR) mass spectrometry were discussed. The fast oscillation could be attributed to the phase-dependent frequency shift resulting from the interference of close peaks. The space charge interaction of ions during the signal acquisitions created an appreciable perturb...

A fast dynamic ion cooling technique based upon the adiabatic invariant phenomenon for Fourier transform ion cyclotron resonance mass spectrometry (FTICR) is presented. The method cools ions in the FTICR trap more efficiently, within a few hundred milliseconds without the use of a buffer gas, and results in a substantial signal enhancement. All per...

An efficient approach for trapping ions and enhancing signal based on 'adiabatic amplitude reduction' for Fourier transform ion cyclotron resonance (FTICR) mass spectrometry is described and evaluated. This method is a modification to the widely used gated trapping technique in which the trapping potential is raised adiabatically rather than instan...

Tandem mass spectrometry (MS/MS) plays an important role in the unambiguous identification and structural elucidation of biomolecules. In contrast to conventional MS/MS approaches for protein identification where an individual polypeptide is sequentially selected and dissociated, a multiplexed-MS/MS approach increases throughput by selecting severa...

When coupled with high-performance capillary separations, Fourier transform ion cyclotron (FTICR) mass spectrometry provides powerful new capabilities for proteomic studies. Selective ion accumulation in a two-dimensional quadrupole device external to an FTICR mass spectrometer has been shown to increase its sensitivity, dynamic range, and duty cyc...

The DNA repair protein XPA recognizes a wide variety of bulky lesions and interacts with several other proteins during nucleotide excision repair. We recently identified regions of intrinsic order and disorder in full length Xenopus XPA (xXPA) protein using an experimental approach that combined time-resolved trypsin proteolysis and electrospray io...

The patterns of gene expression, post-translational modifications, protein/biomolecular interactions, and how these may be affected by changes in the environment, cannot be accurately predicted from DNA sequences. Approaches for proteome characterization are generally based upon mass spectrometric analysis of in-gel digested two dimensional polyacr...

The DNA-repair protein XPA is required to recognize a wide variety of bulky lesions during nucleotide excision repair. Independent NMR solution structures of a human XPA fragment comprising approximately 40% of the full-length protein, the minimal DNA-binding domain, revealed that one-third of this molecule was disordered. To better characterize st...

The coupling of Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) with electrospray ionization has advanced the analysis of large biopolymers and provided the basis for high-throughput protein characterization (e.g., for rapid "proteome" analyses). In this work, the combination of high-performance capillary liquid chromatograph...

The coupling of Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) with electrospray ionization has advanced the analysis of large biopolymers and provided the basis for high-throughput protein characterization (e.g., for rapid “proteome” analyses). In this work, the combination of high-performance capillary liquid chromatograph...

The human liver alcohol dehydrogenase (ADH) isoenzymes are currently believed to play a major role in ethanol metabolism, accounting for most of the ethanol oxidized in the liver. They have similar molecular masses and similar isoelectric point (pI) values (the 13 possible isoenzymes having pIs in the range of 8.26-8.87), making their characterizat...

We report a new tandem mass spectrometric approach for the improved identification of polypeptides from mixtures (e.g., using genomic databases). The approach involves the dissociation of several species simultaneously in a single experiment and provides both increased speed and sensitivity. The data analysis makes use of the known fragmentation pa...

The DNA modifications that lead to mutations are of direct interest for, e.g. the understanding of DNA damage recognition and repair. The characterization of the modified oligonucleotides and enzymatic responses to specific DNA modifications are of primary concern, but also present major analytical challenges. Among the available techniques, mass s...

Complexes of luteinizing hormone releasing hormone (LHRH) with divalent metal ions (Ni, Zn, Cu) have been studied by matrix-assisted laser desorption ionization (MALDI) and Fourier transform mass spectrometry. LHRH-metal complexes were detected in high abundance for all three metals from synthesized samples, particularly in negative ion mode. The m...

Transition metal ion complexes with proteins and peptides are important in many areas of analytical and biological chemistry. We used positive and negative ion MALDI-MS to detect complexes with Cu and Ni ions, and show that the specific and non-specific transition metal ion-peptide complexes can be distinguished by the use of different analytical p...