The researchers demonstrated that antibody aggregates with various sizes and shapes can be observed in solution by using a scanning electron-assisted dielectric microscope (SE-ADM) developed by AIST.

Observation and particle analysis of antibody aggregates in solution

Aggregate analysis technology is increasingly demanded for quality control of biopharmaceuticals that are widely used in the treatment of cancer and autoimmune diseases. In particular, therapeutic antibodies are often manufactured as high-concentration protein solutions and are exposed to various physical and chemical stresses in the manufacturing, storage, delivery, and other processes, and consequently antibodies easily form aggregates. Appropriate evaluation and control of aggregates are essential for the development and manufacture of therapeutic antibodies with guaranteed efficacy and safety. However, it has been a challenge thus far to evaluate aggregates of various particle sizes and shapes using a single analysis method.

The researchers applied SE-ADM developed by AIST in 2014 to observation of antibody aggregates, and demonstrated that aggregates ranging from nanometers (nm) to micrometers (µm) or more in size can be measured as is without drying or staining pretreatment and with a resolution comparable to that of electron microscopy. A wide range of applications can be expected, from basic research in the field of protein science to the development and manufacture of therapeutic antibodies.

The researchers aim to accumulate basic knowledge by creating aggregates under various conditions and investigating the relationship between the physical and chemical stresses on antibody aggregates and the aggregate size and shape.