Publications of Wendy Müller
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See detailStudy of operational parameters on the desorption/ionization and fragmentation of benzylpyridinium ions using gold-capped silicon nanopillars in SALDI-MS
Müller, Wendy ULiege; Far, Johann ULiege; De Pauw, Edwin ULiege et al

Poster (2021, November)

Introduction The use of nanostructured substrates as assisting materials in surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) has gained increasing attention, especially for ... [more ▼]

Introduction The use of nanostructured substrates as assisting materials in surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) has gained increasing attention, especially for analyzing small molecules. Indeed, nanosubstrates usually led to an increased signal reproducibility and a cleaner chemical background in the low m/z range compared to MALDI matrices. However, the understanding of the SALDI process remains incomplete. The impact of the operational parameters on the analyte desorption/ionization (D/I) and fragmentation is of crucial importance in fundamental research and analytical applications. In this study, the survival yield (SY) and D/I of benzylpyridinium (BP) “thermometer” ions were determined during SALDI-MS experiments using a novel nanosubstrate composed of gold-capped silicon nanopillars as a function of several operational parameters. Method Mass spectra of benzylpyridinium ions (p-CH3-BP, 10-4 M in water/acetonitrile 1:1) were acquired between m/z 40 and 260 in reflectron positive ionization mode using a Bruker RapifleX mass spectrometer equipped with a 355-nm SmartBeam3D laser. The influence of several parameters, such as the laser power, footprint and pulse frequency, the number of laser shots, and the duration of the pulsed delay extraction was evaluated. The desorption/ionization (D/I) and survival yields (SY) were calculated for all mass spectra. The D/I is the summation of the intensity of the parent and fragment BP ions. D/I=I_Parent+I_Fragment The SY were determined from the relative intensities of the parent and fragment ions. SY=I_Parent/(I_Parent+I_Fragment ) Preliminary data Gold-capped silicon nanopillar arrays, which are originally designed for Surface-Enhanced Raman Spectroscopy, were tested in SALDI-MS in the perspective of further multimodal analyses. The D/I and SY of BP thermometer ions, and the influence of the operational parameters were studied using these nanosubstrates as assisting materials. In addition to the laser power whose impact has been widely studied using different types of substrates, several other parameters have been tested here: the laser footprint, the laser pulse frequency, the number of laser shots, and the duration of the pulsed delay extraction. Our study suggests that the laser footprint and the pulsed delay extraction have a significant impact both on the D/I and the SY of BP ions, while the number of accumulated laser shots only has an impact on the D/I. On the contrary, the laser shot frequency does not seem to have an impact neither on the D/I nor on the SY. The integrity of the nanosubstrate after the SALDI-MS analyses was also investigated by scanning electron microscopy. This study enables to better understand the fundamental processes underlying SALDI, and to determine the optimal conditions for efficient desorption/ionization of either the BP parent or the fragment by controlling the fragmentation and the nanosubstrate destruction. Indeed, the degradation of the nanosubstrate leads to the formation of interferent ions in the low m/z range. Besides this physicochemical part of the study, the analytical performance of the nanosubstrates was also evaluated. We demonstrated that under optimal conditions no interferent ion was produced alongside the analyte ions in the studied m/z range. On the contrary, the mass spectra acquired with MALDI matrices and gold nanoparticles (AuNPs) were characterized by more background peaks. The nanosubstrates also offer better reproducibility of the signal intensity compared to CHCA and AuNPs, which opens the way for quantification studies. Novel aspects Evaluation of the analytical performance of a SERS nanosubstrate in SALDI-MS and study of the influence of the operational parameters. [less ▲]

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See detailImaging lipids in biological samples with surface-assisted laser desorption/ionization mass spectrometry: A concise review of the last decade
Müller, Wendy ULiege; De Pauw, Edwin ULiege; Far, Johann ULiege et al

in Progress in Lipid Research (2021), 83(101114),

Knowing the spatial location of the lipid species present in biological samples is of paramount importance for the elucidation of pathological and physiological processes. In this context, mass ... [more ▼]

Knowing the spatial location of the lipid species present in biological samples is of paramount importance for the elucidation of pathological and physiological processes. In this context, mass spectrometry imaging (MSI) has emerged as a powerful technology allowing the visualization of the spatial distributions of biomolecules, including lipids, in complex biological samples. Among the different ionization methods available, the emerging surface-assisted laser desorption/ionization (SALDI) MSI offers unique capabilities for the study of lipids. This review describes the specific advantages of SALDI-MSI for lipid analysis, including the ability to perform analyses in both ionization modes with the same nanosubstrate, the detection of lipids characterized by low ionization efficiency in MALDI-MS, and the possibilities of surface modification to improve the detection of lipids. The complementarity of SALDI and MALDI-MSI is also discussed. Finally, this review presents data processing strategies applied in SALDI-MSI of lipids, as well as examples of applications of SALDI-MSI in biomedical lipidomics. [less ▲]

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See detailDual-polarity SALDI FT-ICR MS imaging and Kendrick mass defect data filtering for lipid analysis
Müller, Wendy ULiege; Verdin, Alexandre ULiege; Kune, Christopher ULiege et al

in Analytical and Bioanalytical Chemistry (2021), 413(10), 28212830

Lipids are biomolecules of crucial importance involved in critical biological functions. Yet, lipid content determination using mass spectrometry is still challenging due to their rich structural ... [more ▼]

Lipids are biomolecules of crucial importance involved in critical biological functions. Yet, lipid content determination using mass spectrometry is still challenging due to their rich structural diversity. Preferential ionisation of the different lipid species in the positive or negative polarity is common, especially when using soft ionisation mass spectrometry techniques. Here, we demonstrate the potency of a dual-polarity approach using surface-assisted laser desorption/ionisation coupled to Fourier transform-ion cyclotron resonance (SALDI FT-ICR) mass spectrometry imaging (MSI) combined with Kendrick mass defect data filtering to (i) identify the lipids detected in both polarities from the same tissue section and (ii) show the complementarity of the dual-polarity data, both regarding the lipid coverage and the spatial distributions of the various lipids. For this purpose, we imaged the same mouse brain section in the positive and negative ionisation modes, on alternate pixels, in a SALDI FT-ICR MS imaging approach using gold nanoparticles (AuNPs) as dual-polarity nanosubstrates. Our study demonstrates, for the first time, the feasibility of (i) a dual-polarity SALDI-MSI approach on the same tissue section, (ii) using AuNPs as nanosubstrates combined with a FT-ICR mass analyser and (iii) the Kendrick mass defect data filtering applied to SALDI-MSI data. In particular, we show the complementarity in the lipids detected both in a given ionisation mode and in the two different ionisation modes. [less ▲]

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See detailSurface‐assisted laser desorption/ionization mass spectrometry imaging: A review
Müller, Wendy ULiege; Verdin, Alexandre ULiege; De Pauw, Edwin ULiege et al

in Mass Spectrometry Reviews (2020)

In the last decades, surface‐assisted laser desorption/ionization mass spectrometry (SALDI‐MS) has attracted increasing interest due to its unique capabilities, achievable through the nanostructured ... [more ▼]

In the last decades, surface‐assisted laser desorption/ionization mass spectrometry (SALDI‐MS) has attracted increasing interest due to its unique capabilities, achievable through the nanostructured substrates used to promote the analyte desorption/ionization. While the most widely recognized asset of SALDI‐MS is the untargeted analysis of small molecules, this technique also offers the possibility of targeted approaches. In particular, the implementation of SALDI‐MS imaging (SALDI‐MSI), which is the focus of this review, opens up new opportunities. After a brief discussion of the nomenclature and the fundamental mechanisms associated with this technique, which are still highly controversial, the analytical strategies to perform SALDI‐MSI are extensively discussed. Emphasis is placed on the sample preparation but also on the selection of the nanosubstrate (in terms of chemical composition and morphology) as well as its functionalization possibilities for the selective analysis of specific compounds in targeted approaches. Subsequently, some selected applications of SALDI‐MSI in various fields (i.e., biomedical, biological, environmental, and forensic) are presented. The strengths and the remaining limitations of SALDI‐MSI are finally summarized in the conclusion and some perspectives of this technique, which has a bright future, are proposed in this section. [less ▲]

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See detailMultiplex micro-SERS imaging of cancer-related markers in cells and tissues using poly(allylamine)-coated Au@Ag nanoprobes
Verdin, Alexandre ULiege; Malherbe, Cédric ULiege; Müller, Wendy ULiege et al

in Analytical and Bioanalytical Chemistry (2020), 412(25),

Surface-enhanced Raman scattering (SERS) nanoprobes based on Au@Ag core@shell nanoparticles coated with poly(allylamine) were functionalized with small targeting molecules to evaluate simultaneously the ... [more ▼]

Surface-enhanced Raman scattering (SERS) nanoprobes based on Au@Ag core@shell nanoparticles coated with poly(allylamine) were functionalized with small targeting molecules to evaluate simultaneously the level of expression of two cancer-related markers, both in cells and in tissues. The Au@Ag nanoparticles provide a high SERS signal enhancement in the visible range when combined with resonant Raman-active molecules. The poly(allylamine) coating plays a dual key role in (i) protecting the metal surface against the complex biological medium, leading to a stable signal of the Raman-active molecules, and (ii) enabling specific biofunctionalization through its amine functions. Using small targeting molecules linked to the polymer coating, two different nanoprobes (duplex approach) were designed. Each was able to specifically target a particular cancer-related marker: folate receptors (FRs) and sialic acid (SA). We demonstrate that the level of expression of these targeted markers can be evaluated following the SERS signal of the probes incubated on cells or tissues. The potential overexpression of folate receptors and of sialic acid was evaluated and measured in breast and ovarian cancerous tissue sections. In addition, FR and/or SA overexpression in the tumor region can be visualized with high contrast with respect to the healthy region and with high spatial accuracy consistent with histology by SERS imaging of the nanoprobe signal. Owing to the unique spectral signature of the designed nanoprobes, this approach offers an efficient tool for the spatially resolved, in situ measurement of the expression level of several cancer-related markers in tumors at the same time. [less ▲]

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See detailA molecular imaging approach combining Raman Spectroscopy and Mass Spectrometry to study biological samples
Müller, Wendy ULiege

in Chimie Nouvelle (2020), 38(133), 25-37

The study of biological samples, like biological tissues or microbial communities, can be very complicated as such kind of samples are in essence extremely complex. This complexity is mainly expressed by ... [more ▼]

The study of biological samples, like biological tissues or microbial communities, can be very complicated as such kind of samples are in essence extremely complex. This complexity is mainly expressed by the heterogeneity of their molecular microstructure, both in terms of spatial arrangement and chemical composition. Thus, the analysis of biological samples requires analytical techniques able to visualise the distribution of the chemical compounds within the sample at a molecular level and with a high spatial resolution. To this end, the use of molecular imaging techniques is a promising avenue and, in particular, the development of multimodal approaches (that is, combining several complementary techniques to overcome the limitations of the individual ones) has grown interest in the last decade. Here, we show that the combination of Raman spectroscopy and mass spectrometry imaging represents an up-and-coming implementation of multimodal molecular imaging for the study of complex biological samples. [less ▲]

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See detailMultimodal Molecular Imaging combining Raman Spectroscopy and Mass Spectrometry for the study of biological samples
Müller, Wendy ULiege; Bertrand, Virginie ULiege; Malherbe, Cédric ULiege et al

Poster (2019, November 29)

Biological samples such as tissues, cells or microbial communities including biofilms are intricate molecular systems. Their complexity is mainly expressed by the heterogeneity of their microstructure ... [more ▼]

Biological samples such as tissues, cells or microbial communities including biofilms are intricate molecular systems. Their complexity is mainly expressed by the heterogeneity of their microstructure, both in terms of spatial molecular distribution and molecular composition. Therefore, the analysis of biological samples requires analytical techniques able to visualise the distribution of the molecular components of the sample with a high spatial resolution (down to the single cell level) and with high specificity needed to resolve the complex molecular mixture. However, to date, no single analytical technique used in isolation can fulfil all the required criteria for an optimal imaging analysis of biological samples. Thus, in order to maximise the molecular information and to overcome the limitations inherent to an individual technique, several complementary imaging techniques can be combined in a multimodal molecular imaging approach. In this context, the combination of Raman Spectroscopy and Laser Desorption/Ionisation Mass Spectrometry imaging modalities represents a promising avenue for the study of various biological samples as these techniques respectively offer high spatial resolution and high specificity. Here we show the application of Surface-Enhanced Raman Spectroscopy (SERS) Imaging and Surface-Assisted Laser Desorption/Ionisation Mass Spectrometry (SALDI-MS) Imaging on selected biological samples, namely bacterial biofilms. Both techniques employ nanomaterials to improve the performances of the respective “classical” counterpart technique. In SERS, the deposition of metallic nanoparticles on the sample surface greatly increases the sensitivity by amplifying the Raman signal and leads to the quenching of the sample autofluorescence, which are major drawbacks of Raman Spectroscopy. On the other hand, contrasting with the traditional well-known MALDI-MS, SALDI-MS is a novel technique employing nanostructured substrates instead of organic matrices to promote the desorption and ionisation of the analytes. SALDI-MS represents an interesting alternative to MALDI-MS as the use of nanosubstrates allows to get around the matrix-related issues encountered in MALDI-MS and which can be really problematic during the analysis of metabolites. We showed that SALDI-MS is particularly effective for the analysis of small molecules in both ion modes (negative and positive) with the same nanosubstrates and that the deposition of nanosubstrates instead of an organic matrix provides visually better images with increasing spatial resolution. [less ▲]

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See detailA Mass Spectrometry Imaging approach for the fundamental study of Surface-Assisted Laser Desorption/Ionisation mechanisms
Müller, Wendy ULiege; Malherbe, Cédric ULiege; De Pauw, Edwin ULiege et al

Poster (2019, October)

Surface-Assisted Laser Desorption/Ionisation Mass Spectrometry (SALDI-MS), which employs inorganic nanosubstrates to promote desorption/ionisation of analytes, is a promising technique for the analysis of ... [more ▼]

Surface-Assisted Laser Desorption/Ionisation Mass Spectrometry (SALDI-MS), which employs inorganic nanosubstrates to promote desorption/ionisation of analytes, is a promising technique for the analysis of small molecules. Indeed, SALDI-MS does not require any organic matrix, reducing the desorption/ionisation of interfering organic ions (in low m/z region) and requiring no co-crystallisation, which simplifies the sample preparation. However, while most papers are focused on the development of new nanosubstrates, the fundamental aspects of SALDI-MS have not been studied in detail yet. Indeed, SALDI-MS involves complicated processes, which make the understanding of SALDI-MS desorption/ionisation mechanisms less straightforward. Our study aims at investigating the SALDI-MS processes for various nanosubstrates. We observed that the ionisation of the metallic nanosubstrates occurs during SALDI-MS experiments and that each nanomaterial is increasingly ionised from a different energy threshold. Moreover, the desorption/ionisation and fragmentation of model molecules (benzylpyridinium salts) seem to be correlated with the appearance of the metallic nanosubstrates ions, demonstrating that the nanosubstrate destruction/restructuring may be involved in the desorption/ionisation processes. [less ▲]

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See detailMultimodal molecular imaging combining Raman Spectroscopy and Mass Spectrometry: from fundamental aspects to selected biological examples
Müller, Wendy ULiege

Master's dissertation (2019)

Biological samples are extremely complex molecular systems. Indeed, their molecular microstructure can be very intricate and heterogeneous. Thus, the analysis of such samples requires analytical ... [more ▼]

Biological samples are extremely complex molecular systems. Indeed, their molecular microstructure can be very intricate and heterogeneous. Thus, the analysis of such samples requires analytical techniques providing a high spatial resolution and information on the chemical composition at a molecular level. To this end, the use of multimodal imaging is a promising avenue as it may provide solutions to overcome the limitations of single techniques. The project is devoted to the investigation of multimodal molecular imaging combining vibrational spectroscopy and mass spectrometry, for the study of biological samples, which is of particular interest in the fields of life science, medicine and environment. We first investigated the fundamental desorption/ionisation processes taking place in Surface-Assisted Laser Desorption/Ionisation Mass Spectrometry (SALDI-MS) using various nanoparticles as substrates and p-methoxybenzylpyridinium salt. The amount of detected ions and the observed survival yield in SALDI was found significantly different to what was observed in MALDI. SALDI led to more fragmentation than MALDI, which may complicate the interpretation of SALDI data. We also implemented classical Raman spectroscopy, Surface-Enhanced Raman spectroscopy, MALDI-MS and SALDI-MS imaging on two kinds of biological tissues: a model tissue of mouse brain and a bacterial biofilm. Critical experimental aspects, related to sample preparation, spectral data acquisition and data treatment leading to the generation of molecular images are discussed. [less ▲]

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See detailMetallic nanoparticles: an interesting option for mass spectrometry imaging of small molecules in tissues
Verdin, Alexandre ULiege; Müller, Wendy ULiege; Bertrand, Virginie ULiege et al

Poster (2018, July 05)

MALDI mass spectrometry imaging is a central technique for the visualisation and identification of a wide variety of molecules in biological samples, especially in tissues slides. However, organic ... [more ▼]

MALDI mass spectrometry imaging is a central technique for the visualisation and identification of a wide variety of molecules in biological samples, especially in tissues slides. However, organic matrices used for the desorption and ionisation of molecules suffers from major limitations, particularly for the analysis of small molecules due to interferences from the matrix in the low m/z range. In this preliminary study we compared the performances of 9-aminoacridine, a well known organic matrix used for small molecules anaylsis, and metallic nanoparticles to evaluate the information obtained from both method. Ionisation by nanoparticles is known as Surface-Assisted Laser Desorption Ionisation (SALDI). Metallic nanoparticles seem to be a promising substrate for MS analysis of small compounds in tissues and reveals information that are complementary to those obtained by MALDI. [less ▲]

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See detailDevelopment of nanoprobes for cancerous tissues imaging by Surface-Enhanced Raman Spectroscopy
Müller, Wendy ULiege; Verdin, Alexandre ULiege; Malherbe, Cédric ULiege et al

Poster (2018, May 17)

Early detection and precise characterization of cancers is one of the major challenges in medicine. Consequently, there is a strong need to develop highly sensitive, specific and quick analytical ... [more ▼]

Early detection and precise characterization of cancers is one of the major challenges in medicine. Consequently, there is a strong need to develop highly sensitive, specific and quick analytical techniques. Among the emerging methods allowing the analysis of cancerous samples, Surface-Enhanced Raman Spectroscopy (SERS), an amplified technique of vibrational spectroscopy based on Raman scattering, is particularly suitable. The signal enhancement in SERS, up to 10^12-fold in the presence of metallic nanoparticles near the Raman-active molecule, offers a better sensitivity than in “classic” Raman spectroscopy and thus allows the analysis of molecules in weaker concentrations. One of the advantages of the nanoparticles used in SERS is that they can be functionalized in order to specifically target a molecule of interest and therefore give information about the spatial location of biomarkers via SERS imaging. Our research aims at developing SERS nanoprobes functionalized with folic acid, complementary to the FRalpha receptor (folate receptor alpha), a membrane receptor overexpressed in many types of cancers. SERS imaging with these nanoprobes will then enable to spot cancerous areas within human cancerous tissues and to discriminate between healthy and cancerous tissues. The preliminary results of our study show that nanoprobes can bind to tissues and more particularly at the level of membrane structures and that they can be detected via SERS imaging. SERS imaging also allows to observe a signal accumulation in presumed cancerous areas, in correlation with the histological H&E analysis. Finally, SERS imaging of healthy and cancerous tissues seems to indicate higher signal intensity within cancerous tissues than within healthy tissues. [less ▲]

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