Multimodal Nano-DESI Mass Spectrometry Imaging Reveals Phospholipids Accumulation in and around Amyloid Plaques in Alzheimer's Disease.

Alzheimer's disease (AD), characterized by β-amyloid plaques, is increasingly recognized by lipid dysregulation as a key factor in its pathology. Mass spectrometry imaging (MSI), a powerful tool for mapping the spatial distribution of biomolecules in tissue sections, is ideally suited for investigating region-specific molecular alterations in diseased animal tissues. Recent MSI advancements have revealed plaque-associated molecular features in the AD brain, highlighting the role of metabolic dysfunction in disease progression.

Performance of a Xylazine Test Strip in Urine Biospecimens.

Objective: Herein, we evaluate the performance of xylazine test strips (XTS) in urine samples. XTS is used for community drug checking (powders and liquids) but lacks regulatory approval for human specimen testing.

Methods: We obtained n=85 human urine specimens from a toxicology laboratory in Philadelphia, originally submitted for qualitative mass spectrometry (MS) expanded drug analysis.

Universal Photosensitizer for Isomer-Selective Lipid Imaging with High Molecular Coverage.

Spatial lipidomics is a powerful technique for understanding the complexity of the lipidome in biological systems through mass spectrometry imaging (MSI). Recent advancements have enabled isomer-selected MSI (iMSI) of lipids in biological samples using both online and off-line derivatization strategies. Despite these impressive developments, most iMSI techniques are limited to either positive or negative ion mode analysis, restricting the molecular coverage achievable in a single experiment.

Rapid and Sensitive Detection of Fentanyl and Its Analogs by a Novel Chemiluminescence Immunoassay.

Background: Abuse of fentanyl and its analogs is a major contributor to the opioid overdose epidemic in the United States, but detecting and quantifying trace amounts of such drugs remains a challenge without resorting to sophisticated mass spectrometry-based methods.

Methods: A sensitive immunoassay with a sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high-affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When used with human urine samples, the assay has a sub-picogram limit of detection for fentanyl, with results fully concordant with LC-MS.

A Highly Sensitive and Specific Photonic Crystal-Based Opioid Sensor with Rapid Regeneration.

Opioid misuse and overdose have caused devastating public health challenges and economic burdens, calling for the need of rapid, accurate sensitive opioid sensors. Here, we report a photonic crystal-based opioid sensor in the total internal reflection configuration, providing label-free, rapid, quantitative measurements through change of the refractive index. The one-dimensional photonic crystal with a defect layer that is immobilized with opioid antibodies acts as a resonator with an open microcavity.

Multimodal high-resolution nano-DESI MSI and immunofluorescence imaging reveal molecular signatures of skeletal muscle fiber types.

The skeletal muscle is a highly heterogeneous tissue comprised of different fiber types with varying contractile and metabolic properties. The complexity in the analysis of skeletal muscle fibers associated with their small size (30-50 μm) and mosaic-like distribution across the tissue tnecessitates the use of high-resolution imaging to differentiate between fiber types. Herein, we use a multimodal approach to characterize the chemical composition of skeletal fibers in a limb muscle, the gastrocnemius.

Nano-DESI Mass Spectrometry Imaging of Proteoforms in Biological Tissues with High Spatial Resolution.

Mass spectrometry imaging (MSI) is a powerful tool for label-free mapping of the spatial distribution of proteins in biological tissues. We have previously demonstrated imaging of individual proteoforms in biological tissues using nanospray desorption electrospray ionization (nano-DESI), an ambient liquid extraction-based MSI technique. Nano-DESI MSI generates multiply charged protein ions, which is advantageous for their identification using top-down proteomics analysis.

High-Throughput Mass Spectrometry Imaging with Dynamic Sparse Sampling.

Mass spectrometry imaging (MSI) enables label-free mapping of hundreds of molecules in biological samples with high sensitivity and unprecedented specificity. Conventional MSI experiments are relatively slow, limiting their utility for applications requiring rapid data acquisition, such as intraoperative tissue analysis or 3D imaging. Recent advances in MSI technology focus on improving the spatial resolution and molecular coverage, further increasing the acquisition time.

High-resolution imaging and identification of biomolecules using Nano-DESI coupled to ion mobility spectrometry.

Simultaneous spatial localization and structural characterization of molecules in complex biological samples currently represents an analytical challenge for mass spectrometry imaging (MSI) techniques. In this study, we describe a novel experimental platform, which substantially expands the capabilities and enhances the depth of chemical information obtained in high spatial resolution MSI experiments performed using nanospray desorption electrospray ionization (nano-DESI). Specifically, we designed and constructed a portable nano-DESI MSI platform and coupled it with a drift tube ion mobility (IM) spectrometer-mass spectrometer.

Imaging and Analysis of Isomeric Unsaturated Lipids through Online Photochemical Derivatization of Carbon-Carbon Double Bonds*.

Unraveling the complexity of the lipidome requires the development of novel approaches for the structural characterization of lipid species with isomer-level discrimination. Herein, we introduce an online photochemical approach for lipid isomer identification through selective derivatization of double bonds by reaction with singlet oxygen. Lipid hydroperoxide products are generated promptly after laser irradiation.

Quantitative Mass Spectrometry Imaging of Biological Systems.

Mass spectrometry imaging (MSI) is a powerful, label-free technique that provides detailed maps of hundreds of molecules in complex samples with high sensitivity and subcellular spatial resolution. Accurate quantification in MSI relies on a detailed understanding of matrix effects associated with the ionization process along with evaluation of the extraction efficiency and mass-dependent ion losses occurring in the analysis step. We present a critical summary of approaches developed for quantitative MSI of metabolites, lipids, and proteins in biological tissues and discuss their current and future applications.

A Small-Molecule Modulator of Metal Homeostasis in Gram-Positive Pathogens.

Metals are essential nutrients that all living organisms acquire from their environment. While metals are necessary for life, excess metal uptake can be toxic; therefore, intracellular metal levels are tightly regulated in bacterial cells. , a Gram-positive bacterium, relies on metal uptake and metabolism to colonize vertebrates.

Imaging of Triglycerides in Tissues Using Nanospray Desorption Electrospray Ionization (Nano-DESI) Mass Spectrometry.

Nonpolar triglycerides (TGs) are rarely detected in mass spectrometry imaging (MSI) experiments unless they are abundant in the sample. Herein, we use nanospray desorption electrospray ionization (nano-DESI) to explore the role of the solvent composition and ionic dopants on the detection of TGs in a murine gastrocnemius muscle tissue used as a model system. We evaluated three solvent mixtures for their ability to extract nonpolar TG species: MeOH:HO 9:1 (v/v), MeOH:DCM 6:4 (v/v) and MeOH:AcN:tol 5:3.

Preparative Mass Spectrometry Using a Rotating-Wall Mass Analyzer.

The design of functional interfaces is central to both fundamental and applied research in materials science and energy technology. We introduce a new, broadly applicable technique for the precisely controlled high-throughput preparation of well-defined interfaces containing polyatomic species ranging from small ions to nanocrystals and large protein complexes. The mass-dispersive deposition of ions onto surfaces is achieved using a rotating-wall mass analyzer, a compact device which enables the separation of ions using low voltages and has a theoretically unlimited mass range.

Interactions of poly (anhydride) nanoparticles with macrophages in light of their vaccine adjuvant properties.

Understanding how nanoparticles are formed and how those processes ultimately determine the nanoparticles' properties and their impact on their capture by immune cells is key in vaccination studies. Accordingly, we wanted to evaluate how the previously described poly (anhydride)-based nanoparticles of the copolymer of methyl vinyl ether and maleic anhydride (NP) interact with macrophages, and how this process depends on the physicochemical properties derived from the method of preparation. First, we studied the influence of the desolvation and drying processes used to obtain the nanoparticles.