February Meeting

Speaker: Akos Vertes, The George Washington University

Topic: Spatial Metabolomics of Single Cells in their Natural Environment

Date: February 3, 2025

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Dingyin Tao (owendtao@gmail.com) by Friday, January 31 if you will be attending the dinner.

Abstract: In multicellular organisms, cells assemble into tissues with specific functions. Tissue embedded cells operate a selection of metabolic pathways for the synthesis and degradation of a collection of small molecules that serve growth, signaling, and reproduction. Capturing the spatiotemporal distributions of metabolites, including lipids, with cellular granularity gives new insight into the functioning of tissues. We have developed ambient ionization techniques that can report on the metabolite content of functioning cells with high throughput and targeting capabilities. Image analysis and morphometry of brightfield and fluorescence microscope images is used to target selected cell types, followed by mid-IR laser ablation of individual cells. The ablation plume is ionized by an electrospray (laser ablation electrospray ionization, LAESI). Ion mobility separation (IMS) of the produced ions is followed by time-of-flight or Fourier transform ion cyclotron resonance mass spectrometry (MS) for the determination of cellular metabolite abundances. Cell-type specific small molecule compositions are determined and correlated with active metabolic pathways characteristic to cellular functions. Metabolite abundance distributions reflect population heterogeneity through metabolic noise levels and reveal hidden cellular phenotypes segregated into subpopulations functioning in specific metabolic states. Examples of spatial metabolomics are presented for various cell types including human hepatocytes, Arabidopsis thaliana and Allium cepa epidermal cells, and root nodule cells of Glycine max in nitrogen fixing symbiosis with Bradyrhizobium japonicum. In addition, using MS imaging (MSI) based on MALDI and laser desorption ionization (LDI) from silicon nanopost array (NAPA) nanophotonic platforms, the presence of a wide array of cyclic oligohexoses was discovered in the root nodules with degrees of polymerization in the 2 ≤ n ≤ 14 residue range. The spatial distributions of cyclic oligohexoses in the G. max nodules were established by NAPA-LDI-MSI. They appeared more concentrated at the edge of the infection zone or inner cortex and in the stem. At some locations, possibly in the vascular bundles surrounding the nodule and traversing the stem, the cyclic oligohexoses were especially abundant. At the same time, acyclic oligohexoses with 2 ≤ n ≤ 10 were also detected, and their distributions in the nodule sections were mapped. These linear or branching molecules were abundant in the infection zone, where the cyclic oligohexoses were less concentrated or absent.

January Meeting

Speaker: Kyle Anderson, National Institute of Standards and Technology

Topic: Advancements in methods and instrumentation for HDX-MS and LC-MS

Date: January 13, 2025

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Dingyin Tao (owendtao@gmail.com) by Friday, January 10 if you will be attending the dinner.

Abstract: Subzero temperature chromatography minimizes loss of deuterium during HDX-MS analysis. We developed an HDX-MS chromatography apparatus capable of performing long analytical separations at -30 °C. The apparatus has precise temperature control with two enzyme column compartments held at independent temperatures and allows for rigorous cleaning in parallel to data acquisition to reduce instrument downtime and sample carryover. Methods for both reversed phase and HILIC analytical separations at subzero temperature were developed. HILIC methods developed greatly reduced operational backpressures for easier adoption using any HPLC pumps and enabled virtually water-free separations at subzero temperature. An HPLC pump delivering custom wash solutions to immobilized protease columns was added to replace conventional injections of common wash solutions, which greatly reduce sample carryover and cut necessary blank runs from 5 to 1 for an IgG1 digest. Additionally, methods for automated online removal of phospholipids from membrane proteins will be presented.

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Lightning Talk
Jacob Epstein (NIH/NIA/IRP)

December Meeting

Speaker: Berk Oktem, Food and Drug Administration

Topic: Role of Mass Spectrometry in Chemical Analysis of Medical Device Extractables

Date: December 16, 2024

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Dingyin Tao (owendtao@gmail.com) by Friday, December 13 if you will be attending the dinner.

Abstract: Chemical analysis of medical device extracts has two main purposes: identification of unknown medical device constituents and quantification of known or unknown extractables. Mass spectrometry is an essential part of chemical analysis of medical device extractables. Identification of the extractables is an ongoing challenge with limited options. Quantification is also an important task in this field as the toxicologists, who need this chemical analysis data, make important decisions based on the both the identity and the reported quantities of the extractables. This presentation will attempt to offer a summary of the current status, ongoing research and challenges related to mass spectrometry in this field, and also lists future directions

November Meeting

Speaker: Ed Sisco, National Institute of Standards and Technology

Topic: What’s in My Drugs? – Using Ambient Ionization Mass Spectrometry to Gain Near Real-Time Insights into the Illicit Drug Supply

Date: November 18, 2024

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Dingyin Tao (owendtao@gmail.com) by Friday, November 15 if you will be attending the dinner.

Abstract: Drug overdoses remain near all-time highs, driven by the continued prevalence of synthetic opioids coupled with a constantly changing drug supply. Keeping pace with the drug supply makeup using traditional approaches (i.e., forensic laboratories or toxicology testing) is difficult due to backlogs and lagging spectral libraries. To address these challenges, NIST has worked to establish the Rapid Drug Analysis and Research (RaDAR) program which provides public health and law enforcement entities across the country access to rapid (24 hour) turnaround, comprehensive drug testing using drug paraphernalia residue and ambient ionization mass spectrometry (AI-MS). In this presentation I will discuss our efforts to develop AI-MS methods, libraries, and algorithms that have enabled this measurement capability, what data we are generating and how it is being used, and outstanding data analytic challenges we face. In addition, I will touch on our ongoing research efforts to develop rapid quantitation methods for drug samples as well as a new initiative to bring high-resolution AI-MS to the field through a mobile laboratory platform.
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Gold Sponsor Lightning Talk
Karen Luo, Mid-Atlantic MS Product Specialist
Agilent Technologies, Inc.

October Meeting

Speaker: Gabriella Weiss, NASA

Topic: Measuring intramolecular carbon isotope distributions in amino acids using Fourier transform mass spectrometry

Date: October 14, 2024

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Dingyin Tao (owendtao@gmail.com) by Friday, October 11 if you will be attending the dinner.

Abstract: Molecules form via the addition of single atoms or subunits of atoms and measuring the isotopic composition of different parts of a molecule can provide information about its synthesis as well as alteration by biological and abiotic processes. Molecule fragmentation using mass spectrometry is a common form of compound identification and recently, this has been leveraged to investigate the isotopic composition of specific compound moieties. Historically, intramolecular isotope measurements (i.e., position-specific isotope analysis, PSIA) were laborious, requiring large amounts of analyte and specialized instrumentation. Here, we discuss the use of Fourier transform mass spectrometry (FT-MS) for making molecular average and position-specific isotope measurements. FT-MS (i.e., Orbitrap mass spectrometry) permits the measurement of isotope ratios of intact molecules and their fragments without requiring conversion to simple gases like CO 2 . We focus on the analysis of amino acids and how PSIA of amino acids can be used to distinguish biological and abiotic processes.