Related Experiment Video
Updated: May 13, 2026
10:05
Large-scale Top-down Proteomics Using Capillary Zone Electrophoresis Tandem Mass Spectrometry
Published on: October 24, 2018
Applications of Top-Down Protein Analysis in Clinical Diagnostics
Morgan W Mann1,2,3, Priscilla S-W Yeung1,2, Ruben Y Luo1,2
1Department of Pathology, Stanford University, Stanford, California, USA.
Mass Spectrometry Reviews
|May 12, 2026
Summary
Top-down mass spectrometry (TDMS) and intact mass measurement offer superior protein analysis in clinical labs. These methods accurately identify disease-related protein variants, improving diagnostics and reducing lab times.
Area of Science:
- Clinical Chemistry
- Analytical Biochemistry
- Mass Spectrometry
Background:
- Clinical laboratories increasingly require precise protein analysis for diagnostics.
- Immunoassays and traditional methods face limitations in distinguishing complex proteoforms.
- Proteolysis-aided approaches can be time-consuming for routine clinical testing.
Purpose of the Study:
- To review the clinical applications of top-down mass spectrometry (TDMS) and intact mass measurement for protein analysis.
- To highlight the advantages of these techniques over existing diagnostic methods.
- To discuss the current and future role of TDMS and intact MS in clinical laboratories.
Main Methods:
- Measurement of intact proteins using mass spectrometry without prior digestion.
- Top-down mass spectrometry (TDMS) involves fragmentation of selected intact proteins.
- Focus on analytical techniques enabling high specificity and throughput.
Main Results:
- TDMS and intact MS effectively distinguish pathologically relevant proteoforms from nonpathologic ones.
- These methods offer reduced laboratory turnaround times compared to proteolysis-based techniques.
- Current applications include hemoglobinopathy, myeloma isotyping, transferrin glycosylation, and hormone quantitation.
Conclusions:
- TDMS and intact MS are valuable tools for clinical diagnostics, offering enhanced analytical specificity.
- These techniques are already implemented for various tests requiring high throughput.
- Future clinical testing will likely see expanded use of TDMS for novel diagnostic assays.
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