# A spectroscopic tool for direct chemical structure determination in LC-MS

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $162,457

## Abstract

Project Summary/Abstract
 The overall goal of the proposed project is to develop a new spectroscopy-based technology
that will allow for in situ structural determination of hitherto unknown analytes within the liquid
chromatography-mass spectrometry (LC-MS) framework. The proposed development is built on
the foundation of existing infrared action spectroscopy schemes that provide this capability in a
limited manner within specialized research laboratories, and aims to make it broadly useful for
metabolomic studies, the discovery of new bioactive molecules from natural sources and other
instances where LC-MS is currently used. The specific aims of the project involve developing the
methods and instrumentations necessary to obtain a well-resolved IR spectrum of a mass-selected
analyte for unambiguous structural identification within the short timeframe dictated by LC-MS.
This requires improvements in data acquisition rate of about two orders of magnitude, which will
come from faster wavelength tuning rates and enhanced signal-to-noise ratio. To achieve such
dramatic improvements, a major component of this project involves transitioning from using a
low-repetition-high-pulse-power laser to a high-repetition-lower-pulse-power laser for acquiring
the IR spectrum. This will necessitate a complete redesign of the existing experimental setup and
approach. Moreover, the proposed developments will involve, to our knowledge, the first instance
of applying modulation techniques and lock-in detection to infrared action spectroscopy. If
successful, the proposed project will lead to dramatic enhancements in the capability of mass
spectrometry, pushing it into the realms of NMR in terms of structural elucidation ability while
retaining its high sensitivity, mixture tolerance, and sample throughput rate characteristics. For
example, in natural products research the vast majority of the metabolite signals present in the
mass spectra of a single sample remain structurally unknown due to the extreme cost such detailed
analysis would currently entail. Similarly, in the development of new drugs, new unknown
metabolites are generated and require complete characterization. The proposed developments
would directly address these needs by providing spectroscopically based chemical structure
information within the existing and well-developed LC-MS framework.

## Key facts

- **NIH application ID:** 10021675
- **Project number:** 5R21GM135720-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Etienne Garand
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $162,457
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021675

## Citation

> US National Institutes of Health, RePORTER application 10021675, A spectroscopic tool for direct chemical structure determination in LC-MS (5R21GM135720-02). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10021675. Licensed CC0.

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