Biomedical Engineering Reference
In-Depth Information
3
Principles of MALDI Imaging Mass Spectrometry
MALDI-TOF-IMS allows for the analysis of large numbers of compounds ranging
from small molecular drug and its metabolite molecules ( m/z < 1,000) [ 73, 74 ] to
large proteins with a molecular weight of 10 4 Da [ 75 ] .
3.1
Ionization Methodologies and Instrumentation
for Imaging MS
The ionization methods reported for IMS included MALDI [ 41, 76- 80 ] , Secondary
Ion Mass Spectrometry (SIMS) [ 19, 81- 86 ] , Matrix-enhanced (ME)-SIMS [ 87, 88 ] ,
Desorption Electrospray Ionization (DESI) [ 89- 99 ] , Nanostructure Initiator
Mass Spectrometry (NIMS) [ 100- 102 ] , Atmospheric Pressure Infrared MALDI Mass
Spectrometry (AP-IR-MALDI-MS) [ 103 ] , Laser Ablation-inductively Coupled
Plasma-Mass Spectrometry (LA-ICP-MS) [ 104- 106 ] , Laser Desorption
Postionization (LDPI) [ 107 ], Laser Ablation Electrospray Ionization Mass
Spectrometry (LAESI) [ 108, 109 ], and Surface-assisted Laser Desorption/ioniza-
tion Mass Spectrometry (SALDI) [ 110- 112 ]. Another method was called probe
electrospray ionization (PESI) that was used for both liquid solution and the direct
sampling on wet samples.
The MALDI-MS instrumentation used for IMS included MALDI-TOF, MALDI-
Q-TOF, MALDI-TOF-TOF, MALDI-Q-Ion Mobility-TOFMS (MALDI-Q-IM-
TOFMS) [ 113- 117 ] , MALDI-FT-ICR-MS, MALDI-Ion Trap [ 73, 118- 120 ] , and
MALDI-QIT-TOF [ 121 ] .
3.2
Tissue Sample Preparation
The sample preparation plays a very important role for the analysis of a drug and its
metabolites in biological tissue sections using mass spectrometric imaging. Several
factors in IMS sample preparation must be considered, from sample collection to
surface treatment prior to analysis in order to produce high quality, reliable, and
reproducible results.
The sample preparation procedures for the direct analysis of small molecules in
tissue have been described by several papers [ 120- 124 ]. Tissues (brain, heart, lung,
kidney, liver, etc.), were immediately frozen and stored at −80 °C after harvest. The
frozen tissues were subsequently cut into serial 10-20 mm thick section which was
typically prepared by cryosectioning on a microtome at a temperature of −20 °C.
The adjacent sections were gently mounted onto a conductive surface, MALDI
imaging target plate or glass slides. These plates were desiccated under low vacuum
for a short period of time until dry, then robotically or manually coated with the
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