Direct Tissue Mass Spectrometry Imaging by Atmospheric Pressure UV-Laser Desorption Plasma Postionization

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Biotechnology

Background:

• Atmospheric pressure matrix-assisted laser desorption ionization (AP-MALDI) is a key technique for high-resolution mass spectrometry imaging (MSI) of biological tissues.
• Coupling AP-MALDI with low-temperature plasma (LTP) for postionization significantly enhances sensitivity, improving detection limits for molecular species.
• Matrix-free laser desorption ionization (LDI) methods offer potential advantages by simplifying sample preparation and enabling direct tissue analysis.

Purpose of the Study:

• To report the first results of matrix-free MSI using an atmospheric pressure transmission mode (TM) (MA)LDI source coupled with LTP postionization.
• To evaluate the direct analysis capabilities of this novel setup for imaging lipids in biological tissues without matrix application.
• To compare the performance of matrix-free LDI with conventional MALDI approaches using different matrix application strategies.

Main Methods:

• Development and implementation of an atmospheric pressure (AP) transmission mode (TM) (MA)LDI source.
• Coupling the AP-MALDI source with low-temperature plasma (LTP) for postionization.
• Direct MSI analysis of murine testis tissue sections using the matrix-free approach, followed by comparison with conventional MALDI using matrix applied in various configurations (top, bottom, sandwich).

Main Results:

• Successful matrix-free MSI of murine testis, enabling imaging of diverse lipid classes at 25 μm pixel resolution.
• Demonstration of direct tissue analysis without prior sample preparation beyond sectioning.
• Comparison revealed that sandwich matrix application yielded 2-3 fold higher ion yields than matrix-free or other matrix application methods, indicating the continued benefit of matrix for ion generation.

Conclusions:

• Matrix-free AP-MALDI with LTP postionization is a viable technique for direct MSI of biological tissues, offering high spatial resolution and lipid class imaging.
• While matrix application, particularly the sandwich method, enhances ion yields, matrix-free LDI methods present distinct advantages for ambient laser sampling.
• Postionization strategies significantly improve sensitivity, paving the way for more efficient laser sampling under ambient conditions.