Technology

Overview

Mass spectrometry imaging (MSI) is an effective tool for evaluating the in situ distribution of proteins, peptides, lipids, or metabolites within biological specimens.1,2

Molecular data acquired via MSI provide insights on biochemical variations within clinical specimens that can be correlated with specific histological features and disease states. Hundreds of molecules can be monitored simultaneously to obtain a molecular profile of clinical specimens, and with the use of sophisticated bioinformatics tools, these profiles can be statistically assessed to differentiate between healthy and diseased tissue types as well as to identify molecular distinctions linked to treatment response.

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HGMS Profiling

Histology guided mass spectrometry (HGMS) profiling is a propriety application of MSI, utilized in combination with histopathological analyses for assessing the in situ distribution of targeted biomolecules.3,4 In contrast to whole tissue imaging employed by MSI, HGMS profiling focuses on the direct analysis of histopathologically relevant areas, allowing for the classification of clinical specimens in a high throughput and efficient manner.

Formalin fixed paraffin embedded (FFPE) tissue and fresh frozen tissue specimens are compatible for HGMS profiling. Two (2) serial tissue sections are collected, one is mounted onto a conductive indium-tin oxide (ITO) slide required for HGMS profiling, and the other is mounted onto a standard microscope slide for histological staining.

A qualified physician reviews and annotates the stained section, and the annotated image is merged with the corresponding digital image of the unstained ITO slide. The composite image is subsequently used to target precise tissue locations for analysis. The section is subjected to a specimen preparation method designed for the targeted biochemical class, and a molecular profile is acquired using a Bruker rapifleX™ MALDI TOF mass spectrometer. The resulting molecular profile, also referred to as an average mass spectrum, is statistically analyzed by a clinically validated algorithm to classify the specimen based on the overall distribution and relative intensity of detected biomolecules.

HGMS Workflow Diagram from New River Labs

Clinical MS Profiling

In addition to tissue, clinical mass spectrometry (MS) profiling can be applied to a variety of biological specimens, including biofluids, such as urine, cerebrospinal fluid, and saliva, as well as various cytology specimens. Biofluids are typically concentrated, desalted, and appropriately prepared for the biomolecular class of interest. Specimens are then placed onto a MALDI compatible target for MSI analysis. Cytology specimens, on the other hand, are concentrated onto an ITO slide using a cytospin and processed appropriately. Molecular profiles are attained via a Bruker rapifleX™ MALDI TOF mass spectrometer, and data are analyzed with a validated algorithm to identify patients according to disease state or treatment response.

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MALDI Technology

The Bruker rapifleX™ is a matrix assisted laser desorption/ionization (MALDI) time of flight (TOF) mass spectrometer. Slides containing adhered tissue are directly inserted into the instrument, and a laser is rastered over designated tissue regions causing bombarded molecules to be ablated from the surface and ionized. Charged ions are then accelerated through the flight tube within the mass spectrometer toward the ion detector. Ions with a smaller mass/charge (m/z) ratio move faster through the flight tube than those with a larger m/z value. Because the flight tube is a known length, the “time of flight” correlates directly to the m/z ratio of the ion, which can be calculated using calibration standards of known molecular weight. The resulting mass spectrum displays all observed m/z ions that were detected within a specified mass range.

View MALDI TOF Process

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