# Quadrupole Time-of-Flight LC-MS

> **NIH NIH S10** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $529,999

## Abstract

Abstract
This proposal is for the acquisition of a Bruker timsTOF Pro instrument to be placed in the Proteomics
Shared laboratory Resource (SLR) at the Lerner Research Institute at the Cleveland Clinic. The
Proteomics SLR is equipped with two LC-MS/MS systems including an eight year old ThermoScientific
Orbitrap Elite and a three year old ThermoScientific Fusion Lumos system. The Proteomics SLR is
currently running at capacity, with over 45% of the current experiments involving quantitative proteomic
projects. The current workload of the Proteomics SLR has resulted in long wait times for proteomic
experiments that involve the analysis of more than 20 samples. The large workload and subsequent
wait times are exasperated by the low throughput workflow of the Elite and Lumos instruments, each
instrument analyzing approximately 8 samples per day. The goal of this proposal is twofold and
includes increasing the capacity of the Proteomics SLR and, more importantly, to expand the
capabilities of the SLR to include high throughput proteomic experiments. The timsTOF Pro instrument
is a fast scanning quadrupole time of flight instrument and was selected for this proposal based on
data that indicates that this instrument can analyze between 40-100 samples per day without sacrificing
proteome depth, sensitivity, accuracy and robustness. A comparison of a DIA based proteomic
analysis of a tryptic digest generated from a cell lysate on the Lumos housed in the Proteomics SLR
and the timsTOF Pro instrument showed that the timsTOF Pro quantified more proteins in a 30 minute
gradient (over 4800) compared to a 90 minute gradient on the Lumos instrument (3000). This
increased proteome depth is due to the higher scan rates, 100 Hz, of the timsTOF Pro, along with an
additional dimension of separation (ion mobility), and the capability of this instrument to perform Parallel
Accumulation Serial Fragmentation (PASEF) which allows synchronization of the quadrupole mass filter
with the tims ion mobility cell. There are several studies that would benefit from access to the timsTOF
Pro. These include studies of mouse models of alcohol-associated liver disease and non-alcoholic
associated fatty liver disease (Nagy), the analysis of alterations to the sulhydrome that occur in ageing
(Hine), a study of the signatures that are acutely altered by the gut microbe-derived metabolites TMA and
TMAO (Brown), studies to better understand the mechanisms of glioblastoma (Lathia), identification of
risk factors for major cardiovascular events (Hazen), identification of plasma biomarkers of severe
asthma (Li), and the study of ECM remodeling that occurs in aortic aneurysms (AAA) and osteoarthritis
(Apte).

## Key facts

- **NIH application ID:** 10176802
- **Project number:** 1S10OD030398-01
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Belinda Belle Willard
- **Activity code:** S10 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $529,999
- **Award type:** 1
- **Project period:** 2021-04-15 → 2022-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176802

## Citation

> US National Institutes of Health, RePORTER application 10176802, Quadrupole Time-of-Flight LC-MS (1S10OD030398-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10176802. Licensed CC0.

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