Multiplex MALDI mass spectrometry-based immunohistochemistry
(MALDI-IHC)
on five biomarkers in mouse-brain FFPE sagittal tissue sections. FFPE
tissue sections were stained simultaneously with PC-MT-antibodies
against five different biomarkers, then subjected to MALDI-MSI (in
the positive ion reflector mode). Standard immunofluorescence staining
was also performed on adjacent tissue sections. (a) Colorized five-plex
MALDI-MS image corresponding to the monoisotopic mass reporter m/z values for the following PC-MT-antibodies
(color coding is also noted on the image): myelin (red), NeuN (green),
synapsin (blue), GLUT1 (cyan), and MAP2 (orange). The display scale
(arbitrary peak intensity units), is as follows (minimum intensity/full
intensity threshold): 0/27 (myelin), 0/12 (NeuN), 0/7 (synapsin),
0/8 (GLUT1), and 0/21 (MAP2). The hippocampus (∗) and cerebellum
(⧧) were observed among other brain structures (all MALDI-MS
images have a 20 μm spatial resolution). (b) MALDI-MS image
from an adjacent tissue section stained with a rabbit IgG isotype
control. The rabbit IgG was labeled with the same PC-MT as the rabbit
polyclonal GLUT1 antibody (a mouse IgG isotype control labeled with
the same PC-MT as the mouse monoclonal anti-MAP2 antibody was also
tested with the same results, not shown). (c) Colorized immunofluorescence
overlay of the cerebellum for synapsin (blue), NeuN (green), and myelin
basic protein (red). Immunofluorescence was performed in the “single-plex”
mode on adjacent tissue sections, and images were colorized and overlaid.
(d) Color-coded overlaid MALDI-MS spectra are shown for selected pixels
from the five-plex MALDI-MS image (the pixels are denoted with color-coded
arrows in panel a). Black arrows in the spectra denote the mass reporter
peaks as follows: myelin, 1206.72 m/z (red); NeuN, 1194.67 m/z (green);
synapsin, 894.52 m/z (blue); GLUT1,
1624.80 m/z (cyan); and MAP2, 882.46 m/z (orange). Note that while natural isotopes
of the mass reporters separated by 1 Da are easily resolved by the
MALDI-MS, they are not discernible in the spectra provided due to
the compact x-axis scaling.