Medical Devices

Material Identification in Medical Technology

Problem Statement

The characterization of medical devices or their underlying raw materials often requires the use of a broad spectrum of analytical and physical methods. This involves a significant time commitment.
However, in many cases, quick material information is needed first, which is then refined later with further analyses.

Solution

A versatile method for quickly gaining an overview of a medical device is high-resolution NMR spectroscopy.
It is a method for detailed structural elucidation and quantification of organic substances.
NMR spectroscopy is applicable to all types of organic compounds, including polymers.
Mixtures can be quantified and impurities detected.

Industries & Applications

Medical Technology – Identification of materials and impurities in complex product structures.

Analysis Objectives

Rapid material overview for complex matrices for targeted selection of further test procedures.

Materials

Composite Materials, Product Formulations

Analysis Methods

• ¹H-NMR (Nuclear Magnetic Resonance)

Complementary Methods

• Extraction

Related Issues

• Purity Determinations
• Release Analytics

Example – Heat Patch

In a commercially available heat patch, the active ingredient Nonivamide is detectable in the spectrum after simple extraction with dichloromethane.
However, further information on the carrier liquid (1,2-propanediol),
preservative (4-hydroxybenzoate), adhesive (acrylate), and fabric material (polyester) can also be read from the spectrum.

Example – Warming Ointment

In comparison, a spectrum excerpt (only the aromatic region) of the CDCl₃ extract of a warming ointment is shown.
Even without prior processing of the ointment material, the active ingredients Nicoboxil and Nonivamide
can be identified and approximately quantified despite the presence of the ointment base.

The quantitative ratio of Nicoboxil to Nonivamide is determined from this spectrum to be approximately 91:9,
the package insert for the warming ointment states 86:14.

Medical Technology

Medical technology involves the interaction of materials science disciplines with medicine and pharmacy.
Only through this connection is the development and application of complex medical devices possible.

An example of this is artificial blood purification using hemodialysis. Here – as shown in Fig. 1 – a patient’s blood is passed through a dialyzer outside their body and then returned.
In the dialyzer, toxins are filtered out of the blood through small pores, while vital components remain in the blood.
Further components of a dialysis machine include the blood pump, tubing systems, and measurement and monitoring devices. Additionally, a medication that acts as an anticoagulant can be administered via the dialysis machine.

The various components used here must meet high material-technical and medical requirements.
Important material-related topics include, for example, identity testing and characterization of the plastics used, as well as the investigation of material-related damage cases.

Analytik Service Obernburg possesses many years of expertise and a broad spectrum of methods for physical and chemical testing.
With problem-adapted microscopic, spectroscopic, mechanical, or thermoanalytical investigations – possibly also in suitable combination – a clarification of the respective issue can be achieved quickly and cost-effectively.
Three typical examples are presented below.

Industries & Applications

Medical Technology – Analysis of devices, components, and materials from medical practice.

Analysis Objectives

Failure Analysis and Material Identification of Components and Plastics.

Materials

Membranes, Tubes, Injection Needles

Analysis Methods

• Scanning Electron Microscopy (SEM-EDX)
• IR Spectroscopy
• ESCA / XPS

Example – Defective Capillary Membrane in a Dialyzer of a Dialysis Machine

The filtration behavior of purchased capillary membranes was found to be faulty.
Due to the small structures of the defective hollow fiber membrane, it was examined in cross-section using scanning electron microscopy (SEM) (Fig. 2).
Large voids are visible in the membrane wall. The SEM detailed image indicates that the void is connected to the inner channel (lumen) of the capillary membrane (arrow in Fig. 2).
The large voids reduce the effectively active wall surface of the capillary membrane to up to one third of the normal value, thus representing the reason for the observed reduction in function.

Example – Identification Testing of Plastic Materials

The identification of plastics used in device components such as plastic housings, membranes, or tubing systems is carried out using infrared spectroscopy (FTIR).
The signals in the FTIR spectrum (Fig. 3) can be precisely assigned to the materials used, which is crucial for failure analysis or complaint processing.
The microscopic variant of FTIR analysis is also used for identifying the smallest (from 15 µm in size) organic particles or deposits, e.g., in tubing systems.

Example – Material Surfaces in Contact with Biological Media

For material surfaces (cannulas, membranes, tubes, etc.) that come into contact with body tissue or blood, the surface-sensitive analytical method ESCA/XPS (information depth of a few nm) is preferably used,
to investigate contaminations, coatings, or biocompatibility. An application example is shown in Fig. 4.

Fig. 1 – Principle of Artificial Blood Purification (Hemodialysis)

Fig. 2 – SEM Cross-sectional View of the Damaged Area

Fig. 3: FTIR spectrum of polycarbonate (PC), a material frequently used for transparent housing parts

Fig. 4: Tip of a hollow cannula and the element concentrations found with ESCA in the uppermost nanometers of the cannula’s outer surface, indicating a silicone layer

Polymer Characterization Using GPC – Quality Testing for Plastics

Problem Statement

Even if polymers are composed of the same monomers, their properties can differ. The polymer chains of a material exhibit varying chain lengths or masses. The resulting mass distribution has a decisive influence on the properties of the final plastic.
Conscious or unconscious deviations in the manufacturing procedure can thus lead to undesirable changes and result in processing difficulties or quality defects.
Unsuitable parameters of molding processes can also lead to thermal degradation and thus to a decrease in chain lengths in the product.

Solution

Analytik Service Obernburg offers polymer analyses using GPC (Gel Permeation Chromatography).
In this technique, a sample of the test material is dissolved in a solvent, applied to a separation column, and pumped towards the detector.
The sample molecules are retained to varying degrees depending on their size (more precisely: their hydrodynamic volume) by a special separation material, thus reaching the detector at different times.

Industries & Applications

• Chemical Companies
• Plastics Processors
• Medical Technology

Analysis Objectives

• Assessment of Product Quality

Materials

• Polymers
• Polymers

Analysis Methods

• Gel Permeation Chromatography (GPC)

Related Issues

• Release Tests
• Oligomer Content

Solution

With the help of suitable reference materials of known molecular size, the average molar mass for the sample is finally obtained. This can be calculated in different ways (Mn, Mw, Mz) and thus provides several statistical parameters for production control.
Furthermore, the polydispersity D, which describes the width of the molar mass distribution, is determined. By comparing these parameters for two batches of a product, deviations and process errors can be quickly identified if necessary.

Advantages

At Analytik Service Obernburg, the most common THF-soluble polymers can be analyzed (including PMMA, PS, PC, SAN).
This simple procedure provides timely and meaningful values for quality control or product development.

Fig. 1: Acrylate component of an embedding medium. Among other things, the final hardness is influenced by the average molar mass of the polymer.

Fig. 2: Schematic representation of molecular separation (left) and example of a detector signal for a SAN sample (right)

Fig. 3: GPC system; left: oven containing the separation column(s); center: autosampler and detector; right: pump and solvent reservoir with degassing unit.

Fig. 4: Diagram of the molar mass distribution of a SAN sample, as well as the most important determined molar masses and the polydispersity D.

X-ray Diffraction – Purity Analysis of Bone Substitutes

Problem Statement

The mineral hydroxylapatite – Ca5(OH)(PO4)3 – is a main component of human bone substance and has proven itself as an implant material for surgical applications.
Calcium compounds exist with a similar chemical composition but with a different crystal structure and consequently altered or undesirable properties regarding biocompatibility or resorption rate.

Solution

X-ray diffraction allows the identification and quantitative detection of foreign phases.
For the example shown in Figure 1, the hydroxylapatite contains traces of calcium oxide (marked by reflections with arrows).
The method is described in standard ISO 13779-3.
Another important property that can be determined by X-ray diffraction is the degree of crystallinity of the sample.
Amorphous components demonstrably have higher solubility and can be resorbed more quickly in the body.
An evaluation of the peak width in the diffraction pattern allows conclusions about crystallite size.
The size and shape of hydroxylapatite crystals (HA) are additionally investigated using electron microscopy (see Fig. 2).

Industries & Applications

• Medical Technology

Objectives

Product Development, Quality Assurance, Failure Analysis

Materials

Crystalline Solids, Bone Cements

Analysis Methods

• X-ray Diffractometry (XRD)
• Wide-Angle X-ray Scattering (WAXS)

Complementary Methods

• X-ray Fluorescence (XRF)
• Electron Microscopy

Advantages

X-ray diffraction allows statements regarding phase purity, crystallinity, and crystallite size. These are parameters that must be checked for quality assurance according to standards. In addition to the application example from medical technology, this technique can also distinguish various modifications of the white pigment titanium dioxide or various calcium sulfates (gypsum, bassanite, anhydrite, etc.). For the analysis of hydroxylapatite, Analytik Service Obernburg GmbH also offers the possibility to analyze the Ca:P ratio and heavy metal freedom by X-ray fluorescence (XRF). The ICP-OES method allows the analysis of heavy metal impurities even in the lowest concentrations.

Figure 1: Diffraction pattern of a powder sample plotted as intensity versus diffraction angle (blue line, top). For comparison, below are reflection positions and intensities from a database for hydroxylapatite (green) and calcium oxide (red).

Figure 2: Visualization of the needle structure and size of hydroxylapatite crystals using transmission electron microscopy.

Particle Analysis – Characterization of Powders and Suspensions

Problem Statement

The processing properties of a powder or suspension critically depend on the particle size, particle shape, and surface chemistry of the particles. Thus, one powder may flow finely, while another tends to clump. Particles that are too large can clog filters, while particles that are too small can cause significant dust formation during further processing. This is just a small selection of issues attributable to different particle properties.

Solution

At Analytik Service Obernburg, various analytical methods are used for particle characterization, which will be discussed in more detail below.

Industries & Applications

• Medical Technology
• Paint Manufacturers
• Compounders

Analysis Objectives

• Determination of Particle Size
• Assessment of Particle Shape
• Investigation of Agglomeration Tendency

Materials

• Powders
• Suspensions

Analysis Methods

• Laser Diffraction
• Scanning Electron Microscopy (SEM-EDX)

Example – Particle Size Distribution

The determination of particle size distribution is carried out using laser diffraction. Particles between 0.1 µm and 2000 µm can be measured. A distribution curve is obtained, from which the particle size can be read, as well as various statistical values describing the distribution (Fig. 1). These values can be directly used for validating the manufacturing process in quality assurance. The test is performed on the powder dispersed in water. By measuring with and without ultrasound, a distinction can be made between agglomerates and primary particles.

Example – Particle Shape

Various microscopic measurement methods are available for investigating particle shape – from light microscopy to electron microscopy (SEM) and atomic force microscopy (AFM). These methods allow not only the characterization of the particle’s shape but also its surface fine structure. Both are crucial for the interaction between particles (e.g., agglomeration tendency) (Fig. 2). If required, the particle shape can be quantified by subsequent computer image analysis.

Example – Surface Chemistry

Just as particle shape influences the properties during processing or the distribution of particles in the final product, so does surface chemistry (moisture, foreign substances like oils, or targeted surface modifications). Depending on the specific question, different chemical or spectroscopic methods are used here to detect changes in surface chemistry.

Advantages

The described methods allow for comprehensive characterization and visualization of particles in powders or suspensions. This enables the analysis of raw materials or products within the scope of quality assurance. The methods are also suitable for determining the cause of problems (e.g., during processing) in case of damage. Furthermore, Analytik Service Obernburg possesses extensive expertise for the analysis of catalysts or fillers in solids.

Fig. 1: Particle size distribution of two samples from different production batches.

Fig. 2: Comparison of powders with different agglomeration tendencies