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Minimizing the Coffee Ring Effect: Improving MALDI Dried-Drop Analysis by Sequential Spotting
Joy L Maabadi1, Arbil Lopez1, Joseph H Holbrook1
1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
Journal of the American Society for Mass Spectrometry
|April 8, 2026
Summary
Sequential spotting in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) reduces the "coffee ring effect". This method enhances signal intensity and minimizes analyte heterogeneity in dried-drop analyses.
Area of Science:
- Analytical Chemistry
- Mass Spectrometry
Background:
- Dried-drop analysis in MALDI MS is a common technique for assessing analyte ionizability and fragmentation.
- The "coffee ring effect" causes analyte to concentrate at the edge of dried spots, leading to inconsistent signals and "dead zones".
Purpose of the Study:
- To investigate a novel sequential spotting technique to mitigate the "coffee ring effect" in MALDI MS.
- To improve analyte distribution and signal consistency in dried-drop analyses.
Main Methods:
- Sequential spotting of sample solutions at reduced volumes (halved and quartered pipet solution levels).
- Analysis of dried drops prepared using the sequential spotting method via MALDI MS.
Main Results:
- The sequential spotting technique significantly reduced the diameter of dried spots.
- This method led to enhanced signal intensity and reduced prevalence of "sweet spots" and "dead zones".
Conclusions:
- Sequential spotting is a viable method to improve analyte distribution and signal robustness in MALDI MS dried-drop analyses.
- While increasing preparation time, this technique offers a more reliable approach for sample analysis.
