The 71st American Society for Mass Spectrometry conference drew almost 6,000 people to the George R. Brown Convention Center in Houston last month. The program was chock full of events that ran from 7:00 a.m. to after 10:00 p.m., including the “hospitality suites” provided by the big six mass spec instrument vendors that offer a forum for promotional and technological activities well into the night.
Trending topic
‘Omics was the mainstream of posters and lectures. Focused topics included imaging and high mass molecules, such as IgMs and virus-like particles with mass up to 400 mDa.
Innovation and intelligence are the buzz words that Agilent uses to describe their new Revident LC/Q-TOF instrument. Innovations include temperature control of the vertical TOF flight tube, which improves mass accuracy. A new dynode detector improves resolution and dynamic range, especially at low m/z. The LC/QTOF also includes advanced, modular software for system monitoring and diagnostics of instrument status, including ion optics and electronics, as well as autotune software that can be scheduled for system suitability verification at time slots when the lab is unattended. This helps improve throughput. Agilent’s library of subroutines includes “blank injection” to verify insignificant carry over; “above calibration range” for a hot sample, triggering reduction in sample volume on the re-run, and “auto triggering” of the need for confirmation of analyte identity of using a confirmation run.
Agilent’s 6495 Triple Quadrupole LC/MS instrument offers workflow designed for easy installation, routine use and robust utility. Five supported LC/MS ion sources include Electrospray Ionization (ESI), and Agilent Jet Stream, which uses a sheath of superheated nitrogen for rapid desolvation. This improves lower limit of detection. The 6495 also benefits from Agilent’s intelligent system software that monitors instrument performance in real-time. SWARM autotune software facilitates system start up.
Bruker Daltonics featured the new timsTOF Ultra mass spectrometer, which uses Captive Spray Ionization for single-cell spatial proteomics and lipidomics. The Ultra uses their fourth Generation timsTOF (trapped ion mobility separation) to improve lower detection limit in 4 D (X, Y, Z time) imaging and quantitation. Burker’s applications data shows a maximum false identification rate (FDR) of 1%, and a % CVs <20% with a 0.125 ng protein sample. For LC/MS on the Ultra, Bruker recommends their new VIP-HESI ion source with a 50-um id. This improves lower detection limit and throughput due to shorter gradient elution LC runs.
Omics database
Can a human organ be mapped on a single-cell level to learn about the functionality of each individual cell? And can we learn how different these cells are from person to person? Helmholtz Munich researchers and their collaborators have taken up this challenge and developed the Human Lung Cell Atlas using artificial intelligence (AI)-based techniques. This atlas elucidates the diversity of single lung cell types and allows learning about lung biology in health and disease. It is the first major integrated organ and was built as part of the Human Cell Atlas (HCA) initiative, a worldwide collaborative effort to map the entire body at the level of single cells.
Sample prep automation of pre-omics
Sample prep is the source of most of the variance in LC/MS of biological samples. It is also the most expensive. Shimadzu Scientific Instruments decided to do something about this by automating the many sample prep steps. The CLAM 2040 fully automates the sample prep workflow prior to LC/MS, including sample and reagent pipetting, mixing, heating and vacuum-aided filtration before transferring sample vial to the autosampler. Generally, throughput of manual sample prep ranges from 12 to 60 minutes per sample. Meanwhile, the Clam’s throughput can be as fast as 2.6 minutes per sample.
Most liquid handlers use air driven pipettors to aspirate and dispense liquids. The ePrep Automated Sample Preparation Workstation uses analytical-grade glass syringes for an up to 10x improvement in precision and accuracy even with very volatile or viscous solvents. Positive displacement with a piston is inherently more reliable than using air displacement, especially with low or even sub uL volumes. ePrep’s workstation has a 12-position tool rack consisting of several syringes and tools that are selected and operated with the X,Y,Z overhead arm. Supported functions include pressure driven filtering, solid phase extraction (SPE), vortexing, and magnetic mixing. The system can also perform ultra-low volume liquid-liquid extractions (LLE) that do not require evaporation.
Imaging with MS
Top-down approaches to multi-omics of disease entail analysis of samples derived from hundreds to millions (or more) of cells. At least at the early stage of disease, the cells responsible for the disease are a small fraction, perhaps only one, of the cell population. The signal from a single diseased cell would be swamped out by a background of normal cells. For this reason, researchers have lusted for bottom-up approaches to locate and assay proteins in diseased cells. Over the last five years, advances in MS imaging have enabled location and quantitative analysis of single cells. The data from these assays of single cells is compiled into an atlas of the target organ or infection site. The researcher then compares the biochemistry of normal and diseased cells.
The comparison is not simple. In addition to the background of 10^4 to 10^6 peptides and proteins in each cell, one needs to consider time-dependent variations due to the cell cycle and immunology, which can involve apoptosis. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. Cells are indeed dynamic systems with their own cycle. Dead cells are replaced by similar numbers of new cells.
Imaging with MS is also useful in several applications related to homeostasis. Shimadzu Scientific Instruments introduced the iMScope QT, which combines an optical microscope with Shimadzu 930 Q-TOF MS for spatial ‘omics. The 930 Q-TOF provides rapid, high-spatial imaging of tissue specimens.
Moving down scale a bit, Shimadzu also introduced an imaging kit designed for the MALDI-830 and -820 benchtop MS instruments. These MS instruments feature a fast sample stage and quick load technology. A 200 Hz laser and AeonDetector provide high throughput and long life. The kit includes coated glass slides, slide holder, metal slides and a mask to reduce contamination from adjacent spots during spraying. Software packages include MALDI Solutions and ionView.
At ASMS 2023, I counted 179 of the 2939 posters related to imaging with MS, most frequently with anm instrument that includes a time-of-flight mass analyzer. ToFs are very fast and have exquisite lower detection sensitivity (single ion in the best case).
PFAS was most cited non ‘omics subject
Analysis of PFAS also qualified as a high interest topic at the meeting. Agilent introduced a full workflow including consumables for EPA method 1633 (third draft) for 40 target analytes in soil and wastewater. Agilent’s new 6495 Triple Quadrupole LC/MS is the MS platform of choice. The workflow uses a WAX cartridge for SPE and certified PFAS-free sample vials to ensure that detected analytes came from the sample.
Hydrogen gas for GC/MS
Gas generators are a frequent topic with GC/MS labs primarily due helium price increases. Agilent and Restek have jumped on this with an integrated program to entice and help their MS customers to switch to hydrogen carrier gas. I reported on this in my review of Pittcon 2023. However, after this meeting, I am also impressed with Peak Scientific’s small gas generators for N2 and H2. For example, Peak’s Horizon Nitrogen 24 generator is designed for single quad MS. It provides 99% pure nitrogen with a Pmax of 116 psi. The Horizon uses 55% less energy and is small enough to tuck under a bench. Peak’s H2 generator is even smaller.
The 72ndEdition of this conference series is scheduled for June 2-6, 2024 at at the Anaheim Convention Center in California.
About the Author: Robert Stevenson, Ph.D., is a member of Labcompare's Editorial Advisory Board and Editor Emeritus of Labcompare and American Laboratory. He has been involved in developing instrumentation and enabled applications since the late 1960's at firms including Varian, Altex, Bio-Rad, and TosoHaas. Stevenson has been a regular contributor to American Laboratory since its founding in 1968. He has authored more than 450 papers on new technology and applications.