HyperDSC for Detecting Pure Protein Tgs and Other Weak Transitions

a p p l i c at i o n N o t e
Thermal Analysis
Author
Kevin Menard
PerkinElmer, Inc.
Waltham, MA USA
HyperDSC for
Detecting Pure
Protein Tg’s and
Other Weak
Transitions
Introduction
HyperDSC™ or High Ramp Rate DSC
leads to a significant increase in apparent
sensitivity due to the unique design of the
power compensated DSC. One advantage
of this technique is that very small sample
sizes can be handled, such as pieces of
bio-medical devices collected from inside
a patient or very rare samples. However,
it also increases the ability to detect very
weak thermal transitions from samples.
It has been suggested that certain materials, like pure proteins, have transitions
too weak to be detected by Differential Scanning Calorimetry, because they are
too low energy and/or too broad. HyperDSC provides a viable way of measuring
these weak transitions. Similarly, TMA can be used to measure very weak
transitions and to confirm the data collected by DSC.
Figure 1. HyperDSC run on ova albumin at 100 °C/minute.
Figure 2. Ova albumin protein’s Tg measured by the Diamond TMA.
During our experiment, approximately 5 milligrams of
pure protein, lyophilized from deionized water, were run at
100 °C/min in the Diamond™ DSC, using hermetically sealed
aluminum pans. An Intercooler 2 was used for cooling,
and a nitrogen purge was maintained. Figure 1, shows the
resultant scan on ova albumin. When this run was repeated
at 2 °C/minute, the transition was undetectable even with
larger sample sizes. Similar results were obtained for dried
samples of pure bovine serum albumin (197.88 °C), bovine
gamma globulin (173.53 °C) and Ribonuclease (211.38 °C).
We also applied this methodology to hydroxyethylstarch
(HES: 271.97 °C). In order to confirm these results, the same
samples were analyzed using the Diamond TMA, heating about
10 milligrams in a quartz dilatometer cup at 5 °C/min under
Nitrogen purge. The resulting scans are shown in Figure 2
and correspond well with the data from the DSC. In addition,
we also attempted StepScan™, a temperature modulated
DSC technique, on these materials, heating for the 2 °C
jump at 20 °C/minute and holding for 30 seconds. The
resultant scan for ova albumin is shown in Figure 3.
Again the protein Tg is visible.
Power compensation DSC combined with HyperDSC and
StepScan provide a unique way to identify weak transitions
for compounds traditionally thought to be undetectable by
traditional, heat flux furnace, DSC. Transitions that are hard
to detect in classical DSC are accessible by using more novel
techniques like StepScan and HyperDSC.
Figure 3. StepScan DSC of ova albumin lyophilized from DI water.
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