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How are thermal denaturation and DLS connected?
Thermal denaturation experiments apply a steady
increase in temperature to denature a protein or biologic
candidate, and have long been used as a way to measure
conformational stability. With a thermal denaturation ramp,
you can determine a T
m
, or melting temperature, which is
the temperature at which 50% of the protein is unfolded.
Generally, a higher T
m
is preferable, as it is indicative of
greater stability. Though o en a biologic candidate with
a high T
m
compared to its parent molecule will also have
favourable DLS properties, such as a low PDI, that is not
always the case. Therefore, it is useful to monitor the particle
size and the thermal stability of a biologic in parallel by
collecting both sets of data in the same run.
DLS data and thermal stability
information are not inherently
linked, and can be used for multi-
parameter stability assessment.