Biomarker Research: The Pre-Analytical Puzzle

In the August 17^th issue of PLoS One, Mueller at al. describe the performance of a one-step tissue preservation method that not only maintains tissue morphology but also preserves phosphoproteins and optimizes bio-molecules recovery (full paper).  Anybody who has dealt with the sometimes inextricable problem of choosing a tissue collection and preservation method will appreciate the potential of this new technique.  Indeed, currently available tissue preservation techniques are essentially exclusive, enabling either morphology analysis (e.g. formalin fixing) or proteomic analysis (e.g. snap freezing in liquid nitrogen) but not both.  Being able to use the same tissue sample to perform both types of analysis constitutes, in my mind, a major step forward.

This article reminded me how critical the steps of collecting, processing, and storing bio-samples (aka pre-analytical processes) are to biomarker discovery and development.  Take the following examples I have had to deal with in the past:

• In the Alzheimer’s disease biomarker field, the performance of the amyloid-beta 42 fragment assay is critically impacted by the type of container used for the storage of cerebrospinal fluid samples (the type of plastic used in the manufacturing of the storage container appears to affect differently the recovery of different amyloid-beta fragments; see ADNI Procedure Manual).
• In the immunophenotyping field, the survival and hence recovery of certain leukocyte subsets (e.g. NK cells) is critically affected by the type of collection anticoagulant and the storage temperature of the samples.
• In the cellular immunoassay field, the sample shipment conditions can dramatically affect the outcome of the assay.  Something as simple as shipping blood samples from clinical sites to the testing facility can turn into a nightmare during winter simply because the material freezes in transit.

These anecdotes just give a glimpse of the number of pre-analytical factors that need to be accounted for during biomarker development.  Hence, understanding and defining as early possible the key pre-analytical parameters associated with the conduct of biomarker research is, in my mind, an essential component of a successful biomarker development plan.

Thierry Sornasse for Integrated Biomarker Strategy