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<p>Small metabolites are essential for normal and diseased biological function
but are difficult to study because of their inherent structural complexity.
MALDI imaging mass spectrometry (IMS) of small metabolites is particularly
challenging as MALDI matrix clusters are often isobaric with metabolite ions,
requiring high resolving power instrumentation or derivatization to circumvent
this issue. An alternative to this is to perform ion mobility separation before
ion detection, enabling the visualization of metabolites without the interference
of matrix ions. Here, we use MALDI timsTOF IMS to image small metabolites at high
spatial resolution within the human kidney. Through this, we have found
metabolites, such as arginic acid, acetylcarnitine, and choline that localize
to the cortex, medulla, and renal pelvis, respectively. We have also
demonstrated that trapped ion mobility spectrometry (TIMS) can resolve matrix
peaks from metabolite signal and separate both isobaric and isomeric
metabolites with different localizations within the kidney. The added ion
mobility data dimension dramatically increased the peak capacity for molecular
imaging experiments. Future work will involve further exploring the small
metabolite profiles of human kidneys as a function of age, gender, and
ethnicity.</p></div></div>
Proteoform Differentiation using Tandem Trapped Ion Mobility, Electron Capture Dissociation, and ToF Mass Spectrometry
