New approaches to rapid screening for protein aggregates by light scattering

This paper reports on a recent measurement innovation, the PA M Zero (Protein Aggregation Monitor), that combines state-of-the-art fiber optic technology with a novel measurement chamber to allow as little as 2 μL of protein solution to be analysed while retained in a pipette tip. This eliminates the need to waste scarce sample by dispensing into a cuvette or cell, reduces the need for dilution and prevents cross contamination. Software design has also focussed on making the user interface as simple as possible so that PAM Zero can be used by a bench scientist with minimal training to measure the amount of aggregate present in as little as 4 seconds, reducing the analytical load on central analytical facilities and saving time by rapid rejection of inappropriate samples from the research pipeline. Results from a variety of early studies using PA M Zero and its pre-production prototypes to measure protein aggregation will be presented that demonstrate the benefits of this new method. The paper concludes with suggestions on how to enhance the measurement technology for use in protein structure research using an automated user interface and multivariate analysis algorithms to enable the prediction of suitable crystallisation conditions and accelerate structure determination.