Micro-thermal analysis: scanning thermal microscopy and localised thermal analysis

Abstract

Micro-thermal analysis combines the imaging capabilities of atomic force microscopy with the ability to characterise, with high spatial resolution, the thermal behaviour of materials. The conventional AFM tip is replaced by a miniature heater/thermometer which enables a surface to be visualised according to its response to the input of heat (in addition to measuring its topography). Areas of interest may then be selected and localised thermal analysis (modulated temperature calorimetry and thermomechanical analysis) carried out. Localised dynamic mechanical measurements are also possible. Spatially resolved chemical analysis can be performed using the same basic apparatus by means of pyrolysis gas chromatography-mass spectrometry or high-resolution photothermal infrared spectrometry.

Introduction

Thermal methods of analysis are widely used for the characterisation of pharmaceuticals (Hardy, 1992). The most popular thermal method is differential scanning calorimetry (DSC) which measures the heat flow into or out of a sample subjected to a temperature ramp. In this way transition temperatures can be identified and the enthalpies and heat capacity changes associated with them can be determined. In 1992, Reading and co-workers introduced a temperature modulation combined with a deconvolution of the resulting data (Gill et al., 1993, Reading, 1993, Reading et al., 1993, Reading et al., 1994). This new technique is called modulated temperature DSC (MTDSC). MTDSC significantly improves the sensitivity and resolution of the technique towards some transitions while also enabling their ‘reversing’ or ‘non-reversing’ character to be probed. Observing and quantifying these effects enables the sample’s morphology to be characterised. Initially, MTDSC was restricted to the study of polymers, but recently the technique has been applied to the study of foods and pharmaceuticals (e.g. Barnes et al., 1993, Aldén et al., 1995, Wulff and Aldén, 1995, Bell and Tourma, 1996, Coleman and Craig, 1996, Izzard et al., 1996). MTDSC is particularly suited to the study of glass transitions in amorphous drugs (Craig and Royall, 1998, Hill et al., 1998, Royall et al., 1998).

Another popular thermal method is thermomechanical analysis (TMA) where a probe is placed on a specimen with a given force then, as the temperature is increased, changes in sample length (such as accompany softening during melting) are measured (Riga and Neag, 1991). In this way, thermal expansion coefficients and transition temperatures can be determined. When an oscillating load is applied to the specimen, it is possible to monitor the mechanical modulus and damping of the sample as a function of temperature. This technique is known as dynamic mechanical analysis (DMA) (Reading and Haines, 1995). For these techniques the specimen is typically tens of milligrams or even, in the case of TMA and DMA, larger.

However, the results of such measurements represent the sum of all of the constituents in the specimen. The bulk thermal response is often dominated by the higher concentration of the matrix or substrate material. It is difficult to gain detailed characterisation of dilute components, contaminants and less dominant phases without physically altering the sample. In addition, the experiments are often time-consuming—particularly for thermomechanical and dynamic mechanical tests.

In order to obtain spatially resolved information about a material, the investigator must resort to microscopy. Without employing staining or etching techniques it may be difficult to determine differences in composition across a specimen. Infrared and Raman microspectrometry may be used to investigate chemical composition on a local scale but often the resolution (spatially and structurally) is too poor. Imaging secondary ion mass spectrometry (SIMS) or X-ray photoelectron spectrometry (XPS) can afford similar information but also suffer the same drawbacks in addition to requiring the sample to be in a high vacuum.

The development of the atomic force microscope (AFM) has opened up many new ways of visualising surfaces to very high resolution (Binnig et al., 1986, Wickramasinghe, 1990, Bottomley et al., 1996). A schematic diagram of an AFM is shown in Fig. 1. The instrument consists of a sharp tip mounted on the end of a cantilever which is scanned across the specimen by a pair of piezoelectric elements aligned in the x- and y-axis. As the height of the sample changes the deflection of the tip in contact with the surface is monitored by an optical lever arrangement formed by reflecting a laser beam from the back of the cantilever into a photodetector. The tip is then moved up and down by a feedback loop connected to a z-axis piezo which provides the height of the sample at each x,y position. Besides the topographic information provided by rastering the tip across the sample, other properties can be obtained by measuring the twisting of the cantilever as it is moved across the sample (lateral force microscopy) (Ling and Leggett, 1997). This provides image contrast based on the frictional forces generated from the sample-tip interaction. Other imaging modes, such as force modulation and pulsed force modes can indicate the stiffness of the sample (Rosa-Zeiser et al., 1997).

An advantage of the AFM over the scanning electron microscope is that little sample preparation is required as the sample is not exposed to a high vacuum and electrically insulating materials can be examined. Therefore hydrated, solvent-containing specimens can be imaged. AFM has been used in the biological and pharmaceutical sciences for the imaging of fibrinogen polymerisation, the budding of a virus of an infected cell and the in vitro degradation of polymer surfaces and nanoparticles (Drake et al., 1989, Häberle et al., 1992, Gref et al., 1994, Shakesheff et al., 1994). The atomic force microscope can obtain images fast enough (about 20 s per image) to allow the observation of in situ processes occurring at interfaces and imaging may be carried out with the sample under a thin film of liquid. AFM and DSC have been used to study solid lipid nanoparticles for the controlled delivery of drugs (zur Mühlen et al., 1996). AFM was used to examine the size and shape of the nanoparticles, whilst DSC was used to study the crystallinity of the occluded drug.