Taking imaging to the third dimension

It is a stalwart for the medical sector, but now X-ray CT could breakthrough into the world of product testing. Tom Ray discusses a new technique for 3D imaging

Microstructure affects the performance and characteristics of many products in ways that are not always intuitively obvious. The crunchiness of foods, the hardness of composite materials, the dissolution of tablets, the flexibility of plastics, the strength of refractories and so on are all highly dependent on microstructure. And not surprisingly therefore, microstructural defects are often the root cause of a product's poor performance or outright failure.

[caption id="attachment_24508" align="alignright" width="200" caption="Image 1: A pharmaceutical capsule 'cut' by the technique rather than by actual incision"][/caption]

For the microscopist, charged with the task of understanding microstructure and determining how key parameters contribute to desirable outcomes, and how defects are causing faults, the 'perfect' analytical solution to every investigation would be the work of science fiction. In an ideal scenario, it would be possible to shrink the scientist and allow them to walk around the inside and outside of every material. Here they could go about the business of making measurements of particle size and assessments of the distribution of ingredients. They could determine the porosity of powders or the uniformity of coatings. They could take a good look around a foreign body and examine every structural feature in 3-dimensions, not just the two dimensions afforded by microscopy.

In the absence of a 'shrinkatron' there is another solution that allows the microscopist to carry out investigations of the kind described above. At RSSL, a multi-disciplinary laboratory that offers analytical services to clients in a wide range of industries, X-ray tomography is already proving its worth in new product development and foreign body investigations.

X-ray tomography is a non-destructive technique that is already familiar to many of us through its application in medical imaging. The 3-dimensional images from a CAT scanner are the product of this same technology, although there are some essential differences.

High resolution X-ray CT (computed tomography) differs from conventional medical CAT scanning in its ability to resolve details down to a few tens of microns. The medical CAT scan has a much lower resolution.

[caption id="attachment_24510" align="alignleft" width="200" caption="Image 2: This is a capsule with uneven coating"][/caption]

Where the two technologies are much the same is that both involve taking a sequential set of images through a sample, and using a specialised algorithm to create a three-dimensional reconstruction by layering one image on top of the other. The word tomography comes from the Greek for 'section', so one can see that a multiplicity of thin sections can be layered, one on top of the other, to recreate the fine detail for the whole of a sample's interior and exterior microstructural features. The thickness of the section gives rise to the idea that the CT image is composed of voxels (volume elements) rather than the pixels (picture elements) that describe 2-D images.

As will be obvious from its name, the technique involves exposing a sample to X-rays, which are attenuated i.e. scattered or absorbed by the sample. X-ray attenuation is primarily a function of the incident X-ray energy, density and atomic number of the material being imaged. Hence X-ray tomography can provide imagery and data reflecting both the structure of the material and the distribution of its individual constituents.

However, where X-ray tomography scores over the SEM is that it is applied to the whole sample. Microscopy is limited to looking at a few sections, prepared, quite literally by slicing the sample thinly. Microscopy is destructive, liable to produce artefactual distortions as a consequence of the preparation technique, and ultimately relies on the skill of the microscopist to infer from a few images what is going on with the whole sample.

That is not to dismiss microscopy. There is much it can add to the investigation of foreign bodies and the understanding of microstructure. However, X-ray tomography is much better at presenting a clear picture of what is happening across the whole sample.

Of course, any 3-D image produced by the technique is rendered in two dimensions when published in a magazine! Hence the images shown here can only give a flavour of what the scientists see as they scan a sample. The box drawn around Figure 1 gives some perspective on how particles are distributed within this pharmaceutical capsule. In this particular example, the customer was experiencing some issues with dissolution of capsules, and since the distribution of ingredients, both actives (API) and excipients, is a key factor that determines dissolution properties, it was useful to the customer to understand how well ingredients were dispersed within the product.

[caption id="attachment_24518" align="alignright" width="200" caption="Image 3a,b & c: These represent cuts of a coffee bean across two axes and then a 2D view of how the 3D image gets built up from each consecutive image"][/caption]

It is worth noting that the capsule was viewed whole, but the image itself has been cut. Hence the whole of the capsule is not shown in the image. Also the technique allows for the image to be rotated, expanded, sectioned and otherwise manipulated so that the whole of the capsule can be explored. If the API were concentrated in one region of the capsule this would be immediately obvious, whereas microscopy might miss this fact if the section was taken at the wrong place.

The same observation applies to Figure 2 which shows how uneven coating of a food supplement (a fish oil capsule) has created a weakness and leakage. The manufacturer had received customer complaints so needed to understand exactly where the coating process was failing in order to make changes to the process that would remedy the problem. In fact, X-ray tomography was able to indicate both the thinness of the coating in one region of the capsules, and also an air bubble that could cause weakness.

In some products, air gaps are an advantage, in others they are a problem. Roasting a coffee bean (Figure 3a-c) creates air voids that are crucial to the ultimate flavour release from the coffee. With microscopy, it would be impossible to view how roasting had affected the internal structure of the entire bean. With X-ray tomography, it is simple. Regions of dense packing appear brighter than the air gaps, and the microscopist can 'walk' around the reconstructed 3-D model to get a better appreciation of the depth and breadth of the caverns created by roasting.

In an ideal scenario, it would be possible to shrink the scientist and allow them to walk around the inside and outside of every material

Air gaps are good in coffee beans, bad in materials such as concrete, vital to foams, and depending on size and distribution, important in many foods. The presence of bubbles makes it easier (or even possible) to bite into foods, but there is often a right balance to be struck between too many or too few air gaps. Figure 4 shows the aeration achieved within different formulations of a biscuit that were all cooked in the same conditions. Here the manufacturer was comparing new formulations and needed to understand how the dough was forming or breaking around the air within the biscuit.

Whilst the 2-D images shown here can only give an indication of the 3-D detail afforded by X-ray tomography, anyone familiar with the hospital CAT scan will immediately recognise the benefit of imaging the entirety of a sample rather than just a few sections. It means that important details are not overlooked and rather than inferring the whole picture from a few carefully selected images, one simply sees the whole picture.

Whether looking at the intended microstructural features that explain product performance, or unexpected features such as foreign bodies or microstructural defects, the technique can provide lots of useful information. In some cases, perhaps where packaging cannot be opened, or where foreign bodies should not be removed, it offers a unique and perfect solution for investigating an issue, and is a powerful addition to the microscopist's armoury.

Author: Tom Ray, Laboratory Manager, Microscopy, RSSL

Contact: t: +44 (0)118 918 4000 f: +44 (0)118 986 8932 e: enquiries@rssl.com