Modified target surface to enhance performance during MALDI analysis

Importance of the Topic

The integration of miniaturized, high-density sample preparation with MALDI mass spectrometry addresses growing demands in drug discovery, biotechnology and analytical laboratories. By increasing throughput, reducing reagent consumption and improving sensitivity, such advances enable cost-effective screening of scarce or valuable biological and chemical samples.

Objectives and Study Overview

This work evaluates a novel surface modification on Shimadzu Fleximass™ targets using Aquarray’s Droplet Microarray (DMA) technology. The aim is to enhance MALDI performance by generating omniphilic spots within an omniphobic background, thereby enabling high-density sample arrays and attomole-level detection.

Methodology and Instrumentation

The target surface was patterned into 900 µm diameter hydrophilic spots with 2 025 µm spacing on a stainless steel slide. Nanodroplets of sample and matrix solutions (50–100 nL each) were deposited either manually or via a non-contact dispenser (I-DOT Mini AQ). Matrix used was α-cyano-4-hydroxycinnamic acid (CHCA). Two instruments were compared:

• MALDI-8020 bench-top TOF (Shimadzu)
• MALDImini™-1 bench-top digital ion trap (DIT)

Main Results and Discussion

The patterned target increased sample capacity from 48 to 705 spots. On the MALDI-8020, Glu1-Fibrinopeptide B was detected at 10 amol per spot, a 25-fold sensitivity gain over the specified 250 amol. On the MALDImini™-1, the detection limit reached 50 amol, a 20-fold improvement compared to the 1 fmol specification. Both instruments demonstrated consistent sensitivity enhancements, attributed to reduced spot area, concentrated analyte and minimized matrix suppression.

Benefits and Practical Applications

• Up to 14× higher sample throughput per target
• 20–25× sensitivity improvement enabling attomole detection
• 90% reduction in sample and matrix volume
• Compatibility with automated dispensing for high-throughput workflows

Future Trends and Potential Applications

Further developments may include integration with liquid handling robotics, expansion to alternative MALDI matrices and instruments, as well as coupling to imaging mass spectrometry. The patterning approach could be adapted for on-chip combinatorial chemistry and cellular assays prior to MALDI analysis.

Conclusion

Surface patterning via DMA technology significantly enhances MALDI-MS performance by enabling high-density sample arrays and substantial sensitivity gains on bench-top instruments. This approach conserves sample, accelerates analysis and opens new avenues in high-throughput screening.

Reference

1. Benz M, Asperger A, Hamester M, Welle A, Heissler S, Levkin PA (2020). A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening. Nature Communications, 11, 5391.
2. Benz M, Molla MR, Böser A, Rosenfeld A, Levkin PA (2019). Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening. Nature Communications, 10, 2879.