α‑Cyano-4-hydroxycinnamic Acid and Tri-Potassium
Citrate Salt Pre-Coated Silicon Nanopost Array Provides Enhanced Lipid
Detection for High Spatial Resolution MALDI Imaging Mass Spectrometry
posted on 2021-08-27, 19:33authored byMartin Dufresne, Jarod A. Fincher, Nathan Heath Patterson, Kevin L. Schey, Jeremy L. Norris, Richard M. Caprioli, Jeffrey M. Spraggins
We
have developed a pre-coated substrate for matrix-assisted laser
desorption/ionization (MALDI) imaging mass spectrometry (IMS) that
enables high spatial resolution mapping of both phospholipids and
neutral lipid classes in positive ion mode as metal cation adducts.
The MALDI substrates are constructed by depositing a layer of α-cyano-4-hydroxycinnamic
acid (CHCA) and potassium salts onto silicon nanopost arrays (NAPA)
prior to tissue mounting. The matrix/salt pre-coated NAPA substrate
significantly enhances all detected lipid signals allowing lipids
to be detected at lower laser energies than bare NAPA. The improved
sensitivity at lower laser energy enabled ion images to be generated
at 10 μm spatial resolution from rat retinal tissue. Optimization
of matrix pre-coated NAPA consisted of testing lithium, sodium, and
potassium salts along with various matrices to investigate the increased
sensitivity toward lipids for MALDI IMS experiments. It was determined
that pre-coating NAPA with CHCA and potassium salts before thaw-mounting
of tissue resulted in a signal intensity increase of at least 5.8
± 0.1-fold for phospholipids and 2.0 ± 0.1-fold for neutral
lipids compared to bare NAPA. Pre-coating NAPA with matrix and salt
also reduced the necessary laser power to achieve desorption/ionization
by ∼35%. This reduced the effective diameter of the ablation
area from 13 ± 2 μm down to 8 ± 1 μm, enabling
high spatial resolution MALDI IMS. Using pre-coated NAPA with CHCA
and potassium salts offers a MALDI IMS substrate with broad molecular
coverage of lipids in a single polarity that eliminates the need for
extensive sample preparation after sectioning.