CRM Checks Multi-Layered Coatings with Micrometer-sized
Particles
When doctors put a drug-coated stent into a patient’s artery after clearing a blockage, distribution of micrometer-sized
drug particles in the multiple layers of coatings is critical. Confocal Raman Microscopy (CRM) helps verify that
it’s right.
Stents are typically flexible tubular networks of tiny struts laser-cut from metals such as stainless steel or nitinol.
A coronary stent may be 1.5 – 3 mm in diameter and 15 – 30 mm long. The spacing between struts, particularly
where they join each other, can be as small as 50 µm. Applying coatings to this intricate geometry is a manufacturing
challenge. Coatings containing particles in the 1 µm range must be uniform, free from holes and other defects,
and reproducible within a few weight percent from one stent to the next. Verifying coating quality can also be a
challenge.
For one manufacturer, data gathered with CRM gives them insight into their manufacturing consistency. CRM lets the
manufacturer confirm the distribution of pharmaceutical ingredients, monitor coating thickness and variation, and
also spectroscopically verify the components.
CRM spectral images show sub-surface layers
One advantage of CRM over other analytical methods is the ability to obtain spectral images in three dimensions with
full Raman spectroscopy chemical information. Because the laser excitation energy can penetrate a surface, CRM
lets us peer into the sample non-destructively. This “depth profiling” provides chemical information
from below the surface of the sample in addition to the traditional X-Y planar surface data.
With CRM, spectral data can be collected at every pixel in the scanned area with resolution on the order of 100
nanometers. Information from individual scans can be combined into composite spectral images that dramatically illustrate
the components present in the sample.
Composite image shows distribution
The composite image on this page shows a section of a stent coated with three different components. The coatings
have a total thickness of just over 6 µm, and the sample area in the image is about 40 µm long. The
bottom substrate layer, shown in blue, is a polymer applied directly on the metal of the stent. Over this substrate,
there is a mixture of a copolymer (red) and the active drug product (yellow). This graphical distribution display
was obtained non-destructively, with no cross-sectioning or sample preparation.
Spectra identify components
The plots show the Raman spectra associated with each component. The vertical axis shows spectral intensity, and
the horizontal axis shows the frequency or the Raman shift. Individual components are identified by the differences
in the spectra. The active drug (yellow) is identified by a characteristic profile with unique features not present
in the substrate (blue) or copolymer (red).
Resolution between FTIR and SEM
Confocal Laser Raman Microscopy bridges a gap between Fourier transform infrared (FTIR) spectroscopy with micro-capabilities,
and scanning electron microscopy (SEM). CRM delivers enhanced chemical information from a single instrument in
three dimensions with little to no sample preparation.
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