Graphical Abstract for the TU-Dx project in Analytical Chemistry

Laser desorption/ionization mass spectrometry using MoS2 nanoflakes to (a) study ion formation, (b) improve analytical parameters, (c) develop in vitro assays and (d) multimodal imaging concepts.

2D Materials to Enhance the Performance of Laser-Based Analytical Chemistry

2D layered nanomaterials have triggered high interest in the field of bioanalytical chemistry due to several advantageous properties [1]. In particular the photothermal conversion properties of MoS2 makes it a very promising material for laser desorption/ionization (LDI) and matrix-assisted LDI (MALDI) mass spectrometry (MS) because MoS2 sheet edges are active sites to dissociate H2 and associate H+ supporting by this the formation of protonated and deprotonated molecular ions for bioanalysis [2]. However, so far the fundamental understanding of ion formation under the presence of MoS2 has not been investigated in detail and the importance of basic electron transfer as compared to proton transfer reactions is unknown. Furthermore, the applicability of this promising material for laser-based applications is so far rather unexplored.

Goals

We will evaluate 2D nanomaterial synthesized by our project partners for their potential application for bioanalysis. We will study the initial contribution of the MoS2 nanomaterials to proton transfer reactions occuring during (de-)protonation of molecules in the ionization process and compare this to performance characteristics of conventional MALDI matrices and other functionalized MoS2 materials. Such basic findings are also essential for quantitative analysis of small molecules. This will pave way to a rational approach for functionalized materials with new surface concepts applicable in Analytical Chemistry.

Practically, we will develop ex vivo oxidation assays for tissues and biological fluids to study UV induced oxidations and bifunctionalized MoS2 for cutting-edge multimodal imaging approaches, where established fluorescence imaging [3] will innovatively be combined with MS imaging.

Methods

Pre-engineered MoS2 materials are provided by the TU-D partners. Ion formation will be studied in detail using isotopically labelled analytes to distinguish gas-phase from condensed phase ion formation processes. The analytical scope of the 2D materials will be tested in positive and negative ion mode using standard analytes (small /large, polar/apolar) as well as analytical targets from bio-applications (e.g. metabolites, drugs, peptides) and benchmarked in terms of selectivity and sensitivity against state-of-the-art matrices, MoS2 material (nanoflakes, MoS2/Ag, MoS2/TiS2/SiNW).

Ex vivo assay development will include the use of novel UV sensitive MoS2 surfaces which induce highly localized oxidation reactions in a human skin equivalent giving insight into cell ageing. These developments will be the basis for more complex surface structures facilitating bifunctionalized MoS2, enhancing receptor targeting and imaging capabilities of labelled ligands. Such labels will be fluorescence active but also carry a photocleavable group providing a selective reporter group for LDI MS imaging.

Collaborations

The Eder group will provide point-defected MoS2 films and their characterization. 2D MoS2 flakes and films are provided by Holzer (wet-chemical exfoliation) and Mueller (CVD). Filipovic will model photoexcited electron transport. Holzer will also provide bifunctionalized MoS2 nanomaterial. Libisch will provide theory support for laser-solid interactions. Grasser will connect the  results to device stability/reliability. Biologically relevant material (skin equivalents from cell cultures) will be provided by F. Gruber (Medical University of Vienna).

Supervisor

Martina Marchetti-Deschmann is a specialist in Instrumental Analytical Chemistry focusing on mass spectrometry and hyphenated techniques for biomolecule identification, quantification, detailed characterization and spatial localization. Her research areas include laser-based Analytical Chemistry, in particular laser-assisted Mass Spectrometry (MS). She aims to understand ion formation mechanisms in laser desorption/ionization (LDI) and matrix-assisted LDI (MALDI) MS for sensitive measurements in applications such as imaging MS: She has led research and educational programs strengthening the long-term vision and the future of MS imaging.

Literature

  1. N. Dalila R, M. Md Arshad, S. C. Gopinath, W. Norhaimi, and M. Fathil. Current and future envision on developing biosensors aided by 2D molybdenum disulfide (MoS2) productions. Biosensors and Bioelectronics 132, 248–264 (2019). DOI: 10.1016/j.bios.2019.03.005.
  2. Y. Zhao, G. Deng, X. Liu, L. Sun, H. Li, Q. Cheng, K. Xi, and D. Xu. MoS2/Ag nanohybrid: A novel matrix with synergistic effect for small molecule drugs analysis by negative-ion matrix- assisted laser desorption/ionization time-of-flight mass spectrometry. Analytica Chimica Acta 937, 87–95 (2016). DOI: 10.1016/j.aca.2016.06.026.
  3. D. Xie, D.-K. Ji, Y. Zhang, J. Cao, H. Zheng, L. Liu, Y. Zang, J. Li, G.-R. Chen, T. D. James, and X.-P. He. Targeted fluorescence imaging enhanced by 2D materials: a comparison between 2D MoS2 and graphene oxide. Chemical Comm. 52, 9418–9421 (2016). DOI: 10.1039/c6cc04687h.