Mass spectrometry histochemistry (MSHC) comprises a protocol which renders (neuro)secretory peptides accessible for MS-based imaging in histological sections of formaldehyde-fixed, paraffin-embedded (FFPE) tissue samples [1]. MSHC today is sufficiently sensitive and robust to mine the endogenous peptidomes locked up in the vast archives of clinically well-documented human FFPE materials piled up in biobanks all over the planet.
At ProteoFormiX, peptide biologists, hardware engineers, software developers, and (bio)informaticians work together with (histo)pathology experts and research institute scientists to compile a MSHC Atlas of the FFPE Human Body (Healthy and Diseased). Such FFPE focused supplement to classical histology atlases proves useful in pathological applications, including translational disease biomarker discovery and detection. It is entirely complementary with current parallel initiatives, such as the Human Protein Atlas and the Human BioMolecular Atlas Program.
In total compliance with ethical and GDPR regulations, a wide variety of healthy and diseased tissues of different organs are procured directly from human FFPE biobanks. Neuronal tissues producing well-known neuropeptides (such as the neurohypohysis nonapeptides oxytocin and vasopressin) serve as 'positive controls' for human endogenous peptide MSHC. An automated sprayer is employed for consistent MALDI matrix (dihydroxybenzoic acid) deposition on 5 micron deparaffinized histological sections mounted on regular (non ITO-coated) histology glasses. Multi-Gbyte full-profile HRMS data are acquired on a platform consisting of a hybrid FTMS (ion trap Orbitrap) equipped with an atmospheric pressure MALDI source (MassTech Inc., MD, USA), and analyzed with dedicated software (Mozaic, Spectroswiss), without the need for conversion to imzml.
MSHC allows routine tissue imaging of peptides (as well as metabolites) with high mass accuracy (<1-2 ppm) at <20 micron lateral resolution. Neuropeptide data from hypothalamic nuclei demonstrate that MSHC qualifies as single cell 'omics' technology. Large MSHC data sets representing human neurodegenerative diseases and cancers indicate that MSHC based patient stratification is already feasible today.