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Using a Cyclic Ion Mobility Spectrometer for Tandem Ion Mobility Experiments
Published on: January 20, 2022
Dynamically multiplexed ion mobility time-of-flight mass spectrometry
Mikhail E Belov1, Brian H Clowers, David C Prior
1Biological Sciences Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, USA. mikhail.belov@pnl.gov
Analytical Chemistry
|June 28, 2008
Summary
This study enhances ion mobility spectrometry-time-of-flight mass spectrometry (IMS-TOFMS) for high-throughput proteomics. The developed multiplexing approach significantly improves sensitivity and speed for analyzing complex biological samples like blood plasma.
Area of Science:
- Analytical Chemistry
- Biochemistry
- Mass Spectrometry
Background:
- Ion mobility spectrometry-time-of-flight mass spectrometry (IMS-TOFMS) is valuable for complex biological sample analysis.
- A key challenge is enhancing IMS-TOFMS for high-sensitivity, high-throughput applications, particularly in proteomics.
Purpose of the Study:
- To develop and integrate advanced technologies into IMS-TOFMS for high-throughput analysis of complex biological digests.
- To create a dynamic multiplexing (MP) approach for improved dynamic range and sensitivity in variable sample complexity.
Main Methods:
- Integration of efficient ion accumulation, multiplexing (MP) of ion packets, and advanced analog-to-digital converter signal detection into IMS-TOFMS.
- Development and evaluation of a novel dynamic MP approach correlating analyzer performance with ion source function.
Main Results:
- Reliable detection of peptides at 1 nM in complex matrices with a 3-order dynamic range and <5 ppm mass accuracy.
- Approximately 700 unique peptide identifications from human blood plasma with a projected 4% false discovery rate (FDR) when accounting for IMS data.
- Signal reproducibility >80%, <15% variation in peptide identifications, and 15-minute single sample analysis time.
Conclusions:
- The developed MP IMS-TOFMS system offers a significant advancement for high-throughput, high-sensitivity analysis of complex biological samples.
- The novel dynamic MP approach enhances instrument performance, dynamic range, and sensitivity, addressing variable sample complexity effectively.
- This technology provides a substantial improvement over conventional LC-MS methods for proteomics applications.
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