# Panoptic electrochemical probe for next-generation mass spectrometry based-lipidomics

> **NIH NIH R35** · TEXAS A&M UNIVERSITY · 2021 · $378,750

## Abstract

PROJECT SUMMARY/ABSTRACT
Lipids play a vital role in maintaining cellular function. Altered lipid metabolism is currently considered a hallmark
characteristic of many diseases such as malignancies, neurodegenerative diseases, cardiovascular diseases,
and diabetes. This has led to a demand for new technologies with comprehensive capabilities for revealing lipid
structure and composition. Such technology is essential for the study of lipid structure-function relationships and
the development of methods to diagnose and treat pathologies. Recent efforts in mass spectrometry (MS)-based
lipidomics, including ion activation methods and chemical derivatization, have expanded the toolbox for lipid
analysis. However, there is no single method at present that is capable of resolving all types of lipid structures
since lipids are structurally diverse and often contain mixtures of isomers. The lack of efficient and reliable
analytical approaches for discerning lipid isomers in biological samples directly leads to the fact that the
physiological roles and functions of lipid isomers remain largely unknown. The central vision of my research
program is to address the deficiencies in lipid structural analysis technology using the unique microdroplet
electrochemical (ME) methods, which take advantage of voltage-controlled electrochemical derivatization of lipid
isomers and the dramatically accelerated rates of electrochemical transformations at microdroplet interfaces to
achieve structural elucidation. The proposed voltage-triggered ME reactions will be performed in a modified
electrospray emitter taking the form of a probe and using standard commercial MS instrumentation. Derivatized
products will generate diagnostic ions specific to particular lipid isomers in tandem mass spectra, allowing
characterization of detailed structures. During the next five years, my research group aims to develop ME probes
for lipid analysis with particular emphasis on isomer identification and quantification so as to realize the promise
of ME as a practical research tool for understanding, diagnosing, and treating diseases. A toolbox of ME
reactions will be developed to characterize various lipid isomers including lipid class, acyl chain length, double-
bond positions, geometries, and sn(stereospecific numbering)-positions, the key information needed for accurate
lipid structure annotation. The ME reactions are diverse and can be triggered by voltage changes, so they will
be cascaded into a single system (a panoptic ME probe) to identify lipid structures at all levels of isomer
specificity in a single experimental run. The ME probe will be used for studying the lipidome of pre-diabetic
mouse heart to reveal the initial lipidomic signature in the heart in response to a Western diet and to define the
deleterious effects of lipid isomers on the development of cardiac pathology. The expected outcome of this
project is to provide a widely applicable approach with enhanced capabilities in l...

## Key facts

- **NIH application ID:** 10276837
- **Project number:** 1R35GM143047-01
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Xin Yan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,750
- **Award type:** 1
- **Project period:** 2021-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276837

## Citation

> US National Institutes of Health, RePORTER application 10276837, Panoptic electrochemical probe for next-generation mass spectrometry based-lipidomics (1R35GM143047-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10276837. Licensed CC0.

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