Microfluidics‐based electrospray ionization enhances the intrasource separation of lipid classes and extends identification of individual molecular species through multi‐dimensional mass spectrometry: development of an automated high‐throughput platform for shotgun lipidomics
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Herein, we exploit the use of microfluidics and optimized Taylor cones for improved intrasource separation/selective ionization of lipid classes during electrospray ionization. Increased differential ionization of multiple phospholipid classes was achieved through microfluidics with chip‐based ionization resulting in substantial enhancement of intrasource separation/selective ionization of phospholipid classes in comparison to the conventional ion source. For example, using myocardial lipid extracts, 3‐fold improvements in intrasource separation/selective ionization of myocardial phospholipid classes were routinely realized in the negative‐ion mode in the absence of LiOH or other basic modifiers in the infused sample solutions. Importantly, the relative ratios of ions corresponding to individual molecular species in each lipid class to a selected internal standard from myocardial extracts were nearly identical between the chip‐based interface and the syringe‐pump‐driven capillary interface. Therefore, quantitation of individual lipid molecular species directly from biological extracts through comparisons with internal standards in each lipid class was readily accomplished with an accuracy and dynamic range nearly identical to those documented using the well‐established direct syringe‐pump‐driven capillary interface. Collectively, the use of microfluidics and robotic sample handling substantially enhances intrasource separation of lipids in comparison to routine capillary interfaces and greatly facilitates the use of multi‐dimensional mass spectrometry using shotgun lipidomics, thereby providing an automated and high‐throughput platform for global analyses of cellular lipidomes. Copyright © 2008 John Wiley & Sons, Ltd.
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Rats engineered to carry human APOE2 along with the humanized App gene may offer enhanced modeling capabilities for type III HLP compared to their mouse counterparts.
“Thus, rats, known for their more human-like metabolism compared to mice [54], and engineered to carry human APOE2 along with the humanized App gene, may offer enhanced modeling capabilities for type III HLP compared to their mouse counterparts.”
From Analysis of early effects of human APOE isoforms on Alzheimer’s disease and type III hyperlipoproteinemia pathways using knock-in rat models with humanized APP and APOE (2024) · cites this paper as [54]
The citation is attached to the assertion that rats have more human-like metabolism than mice; the proposed advantage of engineered rats is the citing authors’ own inference. The Experimental section describes mouse tissue preparation, and the Results and Discussion compare lipid-analysis methods, not rat, mouse, and human metabolism. Searches for that comparison and for APOE2, App, and type III HLP found no relevant passage in our copy; page numbers were unavailable. (LLM, conf=0.76)
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Self-citationAnalytical challenges of shotgun lipidomics at different resolution of measurements
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Self-citationSTAT3 activation of SCAP-SREBP-1 signaling upregulates fatty acid synthesis to promote tumor growth
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Self-citationAlterations in Mouse Brain Lipidome after Disruption of CST Gene: A Lipidomics Study
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Self-citation
- Authors
- Han, X., Yang, K., & Gross, R. W.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Han, Xianlin
- Venue
- Rapid Communications in Mass Spectrometry
- Publisher
- Wiley
- Published
- 2008-06-03
- Volume
- 22
- Issue
- 13
- Pages
- 2115-2124
- ISSN
- 0951-4198 (ISSN-L)
- 1097-0231
- PMC
- PMC2927983
- OpenAlex
- W2147240714
- Cited by
- 190
- References
- 36
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 15 · 2023: 9 · 2022: 13 · 2021: 11 · 2020: 11 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 13 · 2015: 9 · 2014: 12 · 2013: 11 · 2012: 24
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Rapid Communications in Mass Spectrometry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P01 HL57278)
- National Institute on Aging and National Institute for Diabetes and Digestive Diseases (R01 AG31675)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrohydrodynamics and Fluid Dynamics
- Keywords
- microfluidics, electrospray ionization, lipid classes, phospholipids, Taylor cone, shotgun lipidomics, myocardial lipids, robotic sample handling, negative ion mode
- MeSH terms
- Equipment Design, Lipids, Robotics, Equipment Failure Analysis, Spectrometry, Mass, Electrospray Ionization, Microfluidic Analytical Techniques
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