Emerging Biomedical Analysis
Lawrence S. Chan, William C. Tang in Engineering-Medicine, 2019
Many variants of ESI have been developed in recent years. Ambient ionization is a family of techniques that was derived from ESI to enable rapid MS analysis at lower cost. Ambient ionization techniques generate ions under ambient conditions for subsequent MS analysis directly on the sample with minimum sample preparation (Cooks et al. 2006, Nyadong et al. 2007). Representative ambient ionization techniques are desorption electrospray ionization (DESI) and direct analysis in real time (DART). In the DESI technique, an electrospray of charged solvent droplets hits the sample surface and extracts analyte molecules to form secondary droplets (Fig. 2). The secondary droplets undergo a similar ionization process with ESI and eventually are delivered to the inlet of a mass spectrometer (Takats et al. 2004). In the DART methodology, an electrical potential is applied to a helium gas stream to generate metastable species. These excited-state gas molecules subsequently react with the analyte surface to form ions (Cody et al. 2005). Due to the simple and cost-effective experimental setup, DESI, DART and other ambient ionization techniques, such as paper spray ionization, liquid microjunction surface sampling probe (LMJ-SSP) and rapid evaporative ionization mass spectrometry (REIMS), were used in several clinical studies (Li et al. 2017). Examples of clinical applications of ambient ionization MS will be discussed later in this chapter.
Lipidomics in Human Cancer and Malnutrition
Qiu-Xing Jiang in New Techniques for Studying Biomembranes, 2020
MSI is an emerging tool in lipidomics research, which allows untargeted analysis and structural characterization of lipids directly from a tissue section. There are several MSI analysis approaches, but the two most common are Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) where DESI-MSI occurs under ambient conditions and MALDI-MSI most often is accomplished under vacuum although atmospheric pressure MALDI is still performed.40–43
Toxicokinetics and Drug Disposition
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
MSI techniques couple the sensitivity and selectivity advantages of MS while preserving the ability to retain spatial relationships within a tissue slice, coupling molecular specificity, quantitation or semi-quantitation, and tissue or cellular localization. Whole-body distribution of parent drug and metabolites can also be determined with MSI, although these studies are currently less routine than classic QWBA studies. The most studied techniques have been liquid extraction surface analysis MSI (LESA-MSI, Swales et al. 2016), desorption electrospray ionization (DESI), matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, and secondary ion MS (SIMS) (Karlsson and Hanrieder 2017). These MSI techniques require a way to “remove” molecules from the tissue slice surface and ionize them for subsequent resolution and detection by the mass spectrometer, and there are several important experimental trade-offs that limit routine application of these methods. All techniques require expensive and sophisticated instruments and analysts. The analytical detection and spatial resolution limits differ for each MSI technique, requiring individual optimization such that the final conditions are often a compromise between sacrificing analytical sensitivity and preserving greater spatial resolution. The choice of MS detection methods (e.g., time-of-flight [TOF] or Fourier transform ion cyclotron resonance [FTICR]) also influences the analytical detection limits and molecular size for the analytes (e.g., peptides). Importantly for the pathologist, spatial resolution ranges differ widely depending on experimental conditions and acquisition times, but in general can be greatest for SIMS (~30 nm to 1 μm), intermediate for MALDI and DESI (~10 to 300 μm) and lowest for LESA-MSI (~200 μm to 1 mm). Solon et al (2010) and Takai and Tanaka (2015) present examples of these techniques applied to drug distribution and toxicology studies while Aichler and Walch (2015) discuss the application of MALDI to problems in pathology.
Approaching complexity: systems biology and ms-based techniques to address immune signaling
Published in Expert Review of Proteomics, 2020
Joseph Gillen, Caleb Bridgwater, Aleksandra Nita-Lazar
Desorption Electrospray Ionization Mass Spectrometry (DESI) MSI operates based on analyte desorption after electrospray ionization focus on the sample surface. In a study by Garza et al., a DESI- field asymmetric waveform ion mobility (FAIMS)-MS tool was used to directly image top down proteins from tissue samples. FAIMS separates ions in their gas phase by their movement in an electric field. It is a useful technique of top-down proteomics to further separate intact structures, downstream of the usual liquid chromatography but in this case, DESI set up. As all analytes in the sample region are transmitted to the MS inlet this coupling reduces signal noise. This group used DESI-MS for top down protein ID of common and biologically relevant proteins like hemoglobin and S100 proteins. Simple sample preparation and top down nature of this approach makes it attractive for proteomic profiling of tissues, but the overall protein coverage of less abundant proteins is apparent in comparison to MALDI-MSI [50].
Role of MALDI-MSI in combination with 3D tissue models for early stage efficacy and safety testing of drugs and toxicants
Published in Expert Review of Proteomics, 2020
Chloe E Spencer, Lucy E Flint, Catherine J Duckett, Laura M Cole, Neil Cross, David P Smith, Malcolm R Clench
Conventional methodologies to localize molecules in tissue samples or in vivo include immunofluorescence microscopy [2], positron emission tomography (PET) [3], and magnetic resonance imaging (MRI) [4]. However, these methodologies have limitations such as requirements for the addition of fluorescent labels, or magnetic or isotopic probes. However, addition of such a probe can have an effect on therapeutic pathways or can alter biological compositions, and additionally such probes have limited use with human subjects. Mass spectrometry imaging (MSI) is an established method which can simultaneously map a variety of molecules within a tissue, without the use of labels. MSI applications extend to a range of ionization techniques including, but not limited to, matrix-assisted laser desorption ionization (MALDI), desorption electrospray ionization (DESI), and liquid extraction surface analysis (LESA). MALDI-MSI is the most widely used technique with high spatial resolution and increasing speed of acquisition, which make it an appealing analytical method for high-throughput drug development studies. The multiplex nature of MALDI-MSI also enables the analysis of different tissue types and biological models for quantitative applications detecting a range of molecules including metabolites, lipids, peptides, and proteins [5–8].
Triolein emulsion enhances temozolomide brain delivery: an experimental study in rats
Published in Drug Delivery, 2021
Won-Bae Seung, Seung Heon Cha, Hak Jin Kim, Seon Hee Choi, Juho Lee, Dongmin Kwak, Hyunwoo Kim, Jin-Wook Yoo, Yong-Woo Kim, Sang Kyoon Kim, Da-Sol Lee
Desorption electrospray ionization (DESI)-MS imaging of biological tissues is an efficient and highly sensitive MS ionization technique for imaging lipids and metabolites from biological tissues (Eberlin et al., 2011). DESI is clinically applicable because it enables the analysis of biomolecules in the x and y directions via spraying of charged droplets and provides chemical information that can be displayed as two-dimensional (2 D) images (Agar et al., 2011).
Related Knowledge Centers
- Ambient Ionization
- Ionization
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- Protein
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- Direct Analysis In Real Time
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- Laser Ablation Electrospray Ionization