There are many different methods to analyse surfaces and interfaces, each with advantages and disadvantages. Imaging plays a key role in medical research and drug discovery, identifying the spatial distribution of particles, locating drug targets, and assessing drug distribution. This type of analysis depends on reliable comparison between different techniques, and developments here can result in more data, gathered more quickly, and in some cases analysis that was not previously possible.
One of these surface analytical techniques, time-of-flight secondary ion mass spectrometry (ToF-SIMS), has advantages including high sensitivity and the ability to achieve high spatial resolution. However, ToF-SIMS generally cannot be used to produce quantitative analyses and traceability is not wellestablished. This hinders its wider use in understanding the causes of diseases and drug uptake within the body. Being able to traceably apply ToF-SIMS to biological samples would improve confidence in results and support a broad range of research, including into Alzheimer’s disease.
The EMRP project Traceable quantitative surface chemical analysis for industrial applications worked on the identification of low concentrations of surface peptides or proteins using liposomes. This involved the introduction of a new diagnostic tissue labelling method for ToF-SIMS, which was traceably linked to an established fluorescent analysis technique.
ToF-SIMS can quantitatively identify different proteins and peptides in a single analysis by using biological labels. Liposomes have enabled ToF-SIMS to be used to simultaneously measure multiple surface sites in a single analysis, introducing the possibility of screening for many different functional entities - proteins, peptides, and DNA in each measurement. Mapping the position of specific peptides simultaneously with other molecules that cannot be located using conventional protein marker imaging, provides information about lipid-protein interactions which are key in understanding the mechanisms of neurodegeneration associated with Alzheimer’s disease.
The benefits of ToF-SIMS, including its superior spatial resolution and the use of samples that are freeze-dried without the need for complex and time consuming preparation, can now be deployed traceably and with confidence for quantitative analysis to identify the location of specific entities on a sample’s surface.
SP Technical Research Institute of Sweden was one of the first to use this technique in determining the amount and location of specific liposome sites on tissue sample surfaces. This is part of their investigations into the formation of Alzheimer’s plaques and tangles. Plaques occur in brain regions where nerve degeneration has occurred due to the disease, and mapping these regions promotes understanding of the mechanisms involved. Studying these characteristic features of Alzheimer’s with greater confidence, and particularly focussing on the spatial localisation of specific peptide deposits will aid research into causes of this disease.
Analysing a single sample to simultaneously look for multiple features means more samples can be studied in greater detail. Samples can now generate more data faster than previously possible, speeding up tissue sample analysis, and reducing costs. Medical researchers can now have greater confidence in using comparable ToF-SIMS data to support their research, contributing to understanding the causes of diseases and drug uptake within the body.