APPLICATION NOTE
Thermal Unfolding of Antibodies
Comparison of nanoDSF and µDSC for thermal stability assessment during
biopharmaceutical formulation development
Dennis Breitsprecher
1
, Nils Glücklich
2
, Andrea Hawe
2
, Tim Menzen
2
1
NanoTemper Technologies GmbH, Munich, Germany
2
Coriolis Pharma Research GmbH, Munich, Germany
Abstract
The assessment of thermal stability parameters of biologics is an integral part
of formulation development in biopharmaceutical research. The ever growing
number of biologics in the development pipelines worldwide demands rapid and
precise methods to quickly screen large sets of conditions in an easy and straight-
forward manner.
In our study, we compare two methods for the detection of thermal unfolding
transition temperatures (T
m
) of a therapeutic monoclonal antibody (mAb):
nanoDSF, which analyzes changes in the fl uorescence emission properties of
proteins, and diff erential scanning calorimetry (µDSC), which detects changes in
the heat capacity of a protein solution upon unfolding. nanoDSF and µDSC both
provide precise and consistent data. nanoDSF in addition overcomes several
limitations by µDSC, such as low throughput and high sample consumption,
and thus represents the ideal technology for rapid and precise thermal stability
screening in biopharmaceutical development.
Introduction
The thermal stability of a protein is routinely used as one main indicator for its
physical stability which aff ects long-term storage in a given formulation. Historically,
µDSC has been used during formulation development. This approach measures