Paper AS+BI-TuM12
Multiplexed Ion Beam Imaging: Cell and Tissue Imaging using Secondary Ion Mass Spectrometry for Pathology

Tuesday, October 23, 2018, 11:40 am, Room 204

Traditional techniques for protein imaging in tissue sections based on light microscopy are limited in the number of simultaneous targets that can be analyzed in a single sample. The need exists in pathology, however, for concurrent imaging of more than just a few of these biomolecules to determine localization of cell types in tissue biopsies. Multiplexed ion beam imaging (MIBI) uses secondary ion mass spectrometry (SIMS) to overcome these limitations and is capable of imaging over 40 biomolecules simultaneously with a spatial resolution greater than many traditional optical and fluorescence microscopy techniques.

In a typical MIBI analysis, a tissue sample is stained with target antibodies conjugated to isotopically pure lanthanide metals. The resulting mass spectra of monoatomic heavy metals exhibit a more characteristic response than the complex mass spectra of fragmented biomolecules typically acquired when analyzing tissue samples with SIMS, the benefit of which being twofold: First, as ion counts from the target analytes are preserved instead of lost due to fragmentation into uncharacteristic species, the generated images have a higher signal to noise ratio. Secondly, now that fragmentation of target analytes is not a limitation, a high current primary ion beam with a tight focus can be employed to image tissue samples with a high spatial resolution at a high throughput rate. Specifically, an oxygen duoplasmatron primary ion beam, focusable down to a spot size of 350 nm, is used in conjunction with a time-of-flight mass analyzer to enable to the simultaneous detection of more than 40 labels at a resolution where individual cells can be differentiated in tissue samples.