W. Richard Bowen and Nidal Hilal 4

6.4 MICRO- ANd NANOTHERMAL CHARACTERISATION wITH SPM 189
B and with previous AFM data, which displayed a behaviour indicative
of adsorbed water at the surface [48].
These and other results not only demonstrate the ability of LTA to thermally
characterise individual components within formulation mixes, but
also highlight the limitation of the system to detect structures of approximately
20 �m � 20 �m or larger, such that if more than one structure
is present in a region, the LTA measurement appears as an intermediate
softening of values between individual components.
Clearly, replacement of the traditional AFM imaging probe with a
heat-conductive Wollaston wire has enabled the local thermal properties
of pharmaceuticals to be investigated but at the sacrifice of spatial resolution.
However, the recent development of a commercially fabricated
doped-silicon cantilever with a heated probe has enabled this problem
to be overcome and for nanoscale thermal events with nanometre precision
to be probed [54]. This nanothermal cantilever has a conductive coating
through which an electrical current is passed to an integrated heater
located directly above the probe. By varying the resistance of the circuit,
the temperature of the heater can be controlled up to 500°C, depending
on the choice of probe. When the probe is in contact with the surface, any
deflections in the cantilever are recorded and this can reveal the nature
of the material (e.g. amorphous versus crystalline) [55, 56] and the occurrence
of thermal phase transitions such as melting or glass transitions [54].
The development of the nanoprobe has also given the ability to maintain
a constant probe temperature during scanning to allow for thermal imaging
of the surface or for controlled thermal nanolithography [57, 58]. An
example of such local thermal analysis is shown in Figure 6.9, where an
Deflection (arb. units)
Dehydration
Melt
50 100 150 200
Temperature (°C)
FIgure 6.9 Nanoscale thermal analysis (NTA) of lactose monohydrate. (Left) Image
recorded with an NTA probe after local thermal analysis has been performed at the area, highlighted
with an arrow. The nanoscale pit is the result of local melting. (Right) Corresponding
cantilever deflection trace, revealing dehydration and melting of the lactose monohydrate.