Space-Resolved Tissue Analysis by Solid-Phase Microextraction Coupled to High-Resolution Mass Spectrometry via...

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Bioanalytical Techniques

Background:

• Desorption electrospray ionization (DESI) is valuable for rapid analysis and imaging of heterogeneous systems.
• Limited exploration of DESI in spatially resolved modes with extractive solid substrates.
• Need for techniques to analyze compound distribution in semisolid and biological tissues.

Purpose of the Study:

• To develop a platform combining solid-phase microextraction (SPME) with desorption electrospray ionization mass spectrometry (DESI-MS).
• To enable unidimensional depth profiling of compound distribution in semisolid systems.
• To evaluate the platform for brain tissue analysis, including xenobiotic distribution and drug release.

Main Methods:

• Development of a custom DESI interface and SPME probe holder to minimize signal instability.
• Quantitative reconstruction of concentration gradients in multilayer gels and surrogate brain tissue models.
• Signal correction using internal standards on SPME fibers and scan-by-scan integration.

Main Results:

• Successful quantitative reconstruction of laminar and radial concentration gradients was achieved.
• Demonstrated good quantitative capability for analyzing xenobiotics in complex models.
• Evaluated suitability for analyzing ex vivo rat brains, confirming the technique's potential.

Conclusions:

• The developed SPME-DESI-MS platform enables fast, noninvasive, and spatially resolved depth profiling of heterogeneous semisolid systems.
• The technique reduces the need for sample slicing and minimizes probe insertions, paving the way for in vivo applications.
• Potential applications include examining spatial drug release patterns in the brain and associated physiological responses.