44
DLS data cannot inherently show you whether the change
in r
H
is due to oligomerization or aggregation, but there
are some general trends. For single protein species,
which are generally in the high nm range for size (see
Page 36), oligomerization events will not generally change
the measured size by an order of magnitude or more.
When you do see large jumps in size, for example from
the 10 to 100 nm range, it's more likely to be amorphous
aggregation. The broadening of size peaks likely indicates
partial unfolding, which also increases the r
H
.
For more in-depth assessment of what a change in PDI
means you may want to also perform other techniques,
particularly those that give information about turbidity and
oligomerization mechanisms. On the other hand, if you
know your particle should be behaving as a monodisperse,
tightly folded species, formulation strategies such as
buffer or additive screening can be applied to reduce
the PDI and enhance the quality profile of your
candidate (see Section 6, Table 2). It may also require an
overhaul of the production or purification process.
