Bruker brings imaging to the masses
accelerate the use of MALDI imaging in drug discovery labs by
simplifying sample preparation procedures.
The new ImagePrep station could enable more people to use the techniques, by simplifying complicated sample preparation procedures. A new software package, flexImaging 2.0, that provides a new, more statistically useful analysis suite has also been launched. MALDI (matrix-assisted laser desorption ionization) is used to find new biomarkers and for studying drug / tissue interactions (pharmacokinetics) in drug discovery as well as for studying biopsies in pathology labs.
Talking to DrugResearcher.com, Dr Detlev Suckau, head of MALDI-applications development and proteomics at Bruker Daltonics, said: "these two advances should improve the uptake of this diagnostic tool which provides information otherwise provided only by long winded histology techniques."
The technique involves taking a section of a biological sample, prepared with a matrix solution; before a pulsed UV (smart beam) laser is scanned over the surface of the sample collecting mass spectra of the ablated ions at every image point. This array of spectra allows analyte specific images to be generated based on selected masses.
One of the major stumbling blocks to the incorporation of MALDI imaging has been the preparation of the tissue, crucial to the resolution and spectral quality. It currently needs expert knowledge to be able to prepare the samples for analysis. There are two protocols currently in use: pneumatic spray and nano spotting.
The problem with the pneumatic spray is its low robustness and poor reproducibility - besides providing poor quality spectra. The technique works by pneumatically spraying the sample with a matrix, which dissolves the surface proteins and makes them amenable to analysis.
According to Dr Suckau: "a wetter surface leads to larger droplets, which dissolve more material and provide better spectra. However, the trade off is that the resolution is determined by the droplet size, so you need to go to a dry regime to get higher resolutions but with poorer spectral quality."
Nano spotting is a sequential technique that is limited by the spot raster size (>100um). Suckau continued: "with the nano spotting technique you get even worse resolution, but better spectra."
The new ImagePrep technique uses vibrations to vapourise the matrix that is gently deposited onto the surface. The deposition of the matrix layer is followed using optical sensors to monitor and control all the preparation parameters. This provides a high reproducibility between samples in a fully automated manner and allows a high spatial resolution, up to 50um, with high quality spectra.
According to Dr Suckau: "the process quality control allows us to reproducibly optimise preparation conditions, we can then reapply the same protocols to sample after sample for best results."
As the technique has become more prevalent, the analysis of large sample sizes has become important. Using MALDI imaging to search for cancerous cells in a single sample can be conveniently achieved using principal component analysis (PCA) in a manner that agrees well with histology measurements.
However, according to Dr Suckau: "you cannot apply the same PCA scheme between different samples as the differences between the two samples are larger than the differences between the tissue types."
The new flexImaging 2.0 software uses a supervised classification approach that uses multivariate statistical methods to classify tissues. Spectra are assigned to known tissue histology and used across a range of different samples to generate a multivariate statistical model that describes the tissue class. This 'Class Imaging' provides good agreement between MALDI imaging results and histology results for a range of sample sources.
