Feature Article

The latest materials testing and analysis techniques are examined. Examples of their use illustrate how they can help in the development of new products, solve product and process issues and ensure quality control.

By: R. White

Comprehensive materials testing is critical in supporting the performance of currently available medical devices as well as developing innovative new ones. Devices such as orthopaedic implants, vascular drug-eluting stents, microelectronics and biomaterials for grafts and cements are all benefiting from enhanced materials technology in metal alloys, advanced ceramics, polymers, biomaterials and composites. These exciting innovations can be correlated to a number of industry trends, the most notable of which are:

Indepth knowledge of critical material characteristics reduces time, cost and risk in medical device design and regulatory approvals. It is, therefore, crucial to have access to the latest and detailed materials evaluation data to make informed decisions on material selection, substitution, qualification and quality assurance (QA) programmes to meet biocompatibility and industry regulations. For manufacturers to maintain high standards of product integrity and assess performance throughout the product lifecycle, techniques for materials testing need to be equally as advanced and powerful. The roles of testing in each stage are:

The techniques toolbox

A wide range of analytical techniques can be used to analyse the composition of advanced materials used to fabricate medical devices. For example, X-ray diffraction (XRD) and X-ray fluorescence (XRF) can be employed in metallurgical testing through to bulk sample analysis. Scanning electron microscopy (SEM) can provide a high resolution overview of the surface. X-ray photoelectron spectroscopy (XPS) (Figure 1) is employed in surface analysis and provides quantified elemental and oxidation-state information. Time-of-flight secondary ion mass spectrometry (ToFSIMS) reveals detailed molecular information from the outer nanometres of the surface. Both XPS and ToFSIMS can also be used in an imaging mode to gain an insight into the spatial distribution of chemical and molecular species. Topographical parameters such as surface roughness and microfeatures can be determined by white light interferometry techniques.

The most advanced materials analysis techniques have played an important role in the development of, and brought new insight into, the validation of cleaning methods. These include examination of surface contamination or marks on implants, low-volume residual gas analysis of packaging, ageing studies of cardiovascular stents, and the development of new cleaning and passivation methodologies and QA/quality control of raw materials and coatings on devices.

Conformity testing

Legislation drives decontamination, quality, validation and sterilisation of medical devices. Regulatory authorities demand a high degree of QA and validation. Analytical testing may often be part of batch conformity testing, which could range from ensuring the consistency of the raw material or precursor parts to testing the final parts. A typical analysis can involve chemical analysis to ensure that deleterious or toxic elements are excluded and analysis of physical properties such as particle size, shape and strength. Many testing protocols will involve multiple tests to confirm a range of indicative performance properties. In the case of synthetic bone material, which contains calcium phosphate, conformity testing would include chemical and mineralogical analysis. Calcium phosphates produce different crystal forms such as hydroxyapatite, α-tricalcium phosphate and β-tricalcium phosphate, each of which behaves and reacts differently; therefore, it is essential to ensure that the correct form is being manufactured or used as a precursor (such as a coating). XRD is used to discern the crystal lattice structure of the different forms.

Chemical analysis will be routinely conducted on products and intermediaries to ensure that the correct ratios of material have been used. XRF would be the technique of choice for inorganic components such as alumina and zirconia; however, detection limits for XRF are generally limited to 0.01% or 0.02% and, therefore, cannot detect trace levels of potentially toxic elements at the ppm levels. Techniques such as inductively coupled plasma spectrophotometry would be used after chemical dissolution to measure trace toxic elements.

In general, QA programmes are bespoke and only occasionally are they predefined for a medical device application and material. Some materials used for surgical implants are covered by international standards. For example, zirconia for implants is covered by ISO 13356 Implants for Surgery, Ceramic Materials Based on Yttria-Stabilised Tetragonal Zirconia, which defines standardised testing protocols and minimum acceptance criteria. In the case of the zirconia, it includes other parameters such as strength, fatigue, radioactivity and ageing.

Sources of contamination

Contamination can be divided into two categories: contamination that originates from the process (inherent) and the type that originates from outside the process (foreign). During manufacture, medical devices come into contact with numerous chemical species such as shot or grain blasting, polishing media, lubricants and cutting fluids that could serve as contaminants. Likewise, passivation by nitric or citric acid can introduce additional contaminants before the product undergoes a cleaning regime, which ironically may itself add contaminants to the surface such as deposits from the water source and detergent residues.

These deposits can be identified using a combination of XPS and ToFSIMS to obtain true nanometre surface chemistry. Surface analysis techniques can be used to directly measure the surface composition at each process step to identify and quantify any deposits and residues remaining on the surface of the implant. In this way manufacturers can ensure that the necessary cleanliness standards are met and their cleaning regimes are effective.

Measuring cleanliness

Figure 2. (click to enlarge) Cleanliness index of a titanium hip stem.

A validation tool, known as the Validata Index, has been developed that reports the complex surface cleanliness data in the form of a single figure that is quantifiable and comparable. Derived from a complex algorithm, the index offers a simple comparison between samples and permits the monitoring of process trends. Weekly monitoring of the cleaning process allows for problems to be quickly identified, the source investigated and corrective action implemented. It is now used routinely in a number of medical device processes such as the evaluation of each step in a multistep procedure, quantifying surface modification, checking oxide layer build-up, monitoring plasma deposition and passivation monitoring. It can also be used to determine if changes to cleaning or manufacturing processes improve or degrade surface cleanliness. Monitoring of this type is an essential tool for ensuring that production process changes do not compromise surface cleanliness or affect performance in use and that production time is kept to a minimum (Figure 2).

Contamination that arises from foreign sources during medical device manufacture and/or packaging can have dramatic consequences. Some forms of contamination such as fibres and gross deposits can be readily observed, but others such as thin films and incorrect coating composition can only be detected by sensitive analytical techniques. Scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDX) with microanalysis can be employed to examine and analyse contaminant fibres, particulates and deposits identified during manufacture/inspection. These techniques supply an image of the contaminant, including its size, shape and morphology, together with chemical analysis information. Suspect materials can then be “fingerprinted” and comparisons made to pinpoint the source of contamination. XPS and ToFSIMS are most utilised for the identification of thin film contamination and investigations into coating composition. Combining data from these two techniques gives quantified elemental and oxidation-state information as well as detailed molecular information from the outer nanometres of the surface. For example, in the examination of metal implants such as hip stems, contamination can be in the form of detergent residues from the cleaning process. Once the contaminant has been identified, the suspect materials can be isolated and comparisons made to identify and eliminate the source of the problem.

Figure 3. (click to enlarge) Quantified spectral and imaging elemental and oxidation state surface information from the outer nm of the surface to a 1μm depth.

Material surface analysis plays an important role in passivation and chemical coatings of devices. For example, in the case of a permanent or semipermanent implant (such as a metal or ceramic implant, synthetic bone material, a stent or some active electrical or electronic device), it is the surface of the device that is the physical interface with the patient’s tissues; therefore, the highest standards of surface integrity and clinical cleanliness must be achieved (Figure 3).

It is also appropriate for surface analysis measurements to be used to examine both surfaces that come into contact with implants before they are installed and any residues that may be left by cleaning processes. Clearly, when assessing potential contamination down to the molecular level, the surface data obtained can be incredibly complex and often requires a high level of expertise to interpret. For chemical analysis of surfaces, a variety of technologies are available including secondary ion mass spectrometry, which examines the chemical composition of surfaces and subsurfaces using a depth profiling technique that examines how elemental composition varies with depth.

Surface morphology

As well as chemically distinct zones, surfaces exhibit differences in physical properties surface roughness, surface finish wear or machining details. One of the most recent technologies for examining physical microfeatures is three dimensional (3D) noncontact profiling (3DP), which utilises white light interferometry techniques. This allows areas from a few square microns up to the centimetre scale to be analysed with nanometre resolution. White light 3DP is a noncontact topographical measurement technique analogous to AFM and stylus measurement systems. With nanometre resolution in the z-axis and micron resolution in the x and y axes, 3DP provides 3D quantified images of the surface from which features such as roughness, particulates, holes and deposits can be accurately measured. Topographical parameters such as surface roughness can be determined over areas not just lines. In addition, 3D-scanning electron microscopy can be used to interrogate the surface physical structure at high resolution.

Properties investigated by 3DP include surface finishing issues such as polishing, machining or grit blasting, roughness measurements, checking uniformity of coatings. Etching of components by aggressive environments can be examined to understand rates and mechanisms of degradation.

Realising the future

Comprehensive physical and chemical analysis of materials and their surfaces is critical to the ongoing development of new devices and improvement of older systems. Having access to the latest analytical techniques can improve product performance and QA. In addition, the suitability of production environ- ments is essential in realising the next generation of devices and materials, which may include technologies that extend life times, mimic natural materials more closely and allow size minimisation.

Dr Richard N. White is Senior Manager Testing and Environmental at CERAM, Queens Road, Penkhull, Stoke-on-Trent ST4 7LQ, UK, tel. +44 845 026 0902, e-mail: richard.white@ceram.com, www.ceram.co.uk