<?xml version="1.0" encoding="utf-8"?>
<export-example>
  <doc>
    <id>38272</id>
    <completedYear/>
    <publishedYear>2016</publishedYear>
    <thesisYearAccepted/>
    <language>eng</language>
    <pageFirst>041001-1</pageFirst>
    <pageLast>041001-10</pageLast>
    <pageNumber/>
    <edition/>
    <issue>4</issue>
    <volume>11</volume>
    <type>article</type>
    <publisherName>AVS: Science &amp; Technology of Materials, Interfaces, and Processing</publisherName>
    <publisherPlace/>
    <creatingCorporation>AVS: Science &amp; Technology of Materials, Interfaces, and Processing</creatingCorporation>
    <contributingCorporation/>
    <belongsToBibliography>1</belongsToBibliography>
    <completedDate>--</completedDate>
    <publishedDate>--</publishedDate>
    <thesisDateAccepted>--</thesisDateAccepted>
    <title language="eng">Improved 3D-imaging of a sirolimus/probucol eluting stent coating using laser postionization secondary neutral mass spectrometry and time-of-flight secondary ion mass spectrometry</title>
    <abstract language="eng">Implantable drug delivery systems that provide controlled and sustained release of a therapeutic agent are used in a wide variety of applications. Drug eluting stents, which are used to treat coronary artery disease, are among the most widespread of these devices, with an estimated 3x10⁶ implants annually worldwide. Controlling the rate of drug release from these devices relies on precise control of the three dimensional (3D)-distribution of the drug, so methods for measuring this distribution are of great importance. The aims of this work were to determine how 3D-imaging of polymer-free sirolimus/probucol drug eluting stent coatings could be improved through the use of laser postionization secondary neutral mass spectrometry (Laser-&#13;
SNMS) and Ar cluster sputtering with time-of-flight secondary ion mass spectrometry (ToF-SIMS) and to optimize conditions for this analysis. In this study, 3D-imaging of a sirolimus/probucol dual drug eluting stent has been investigated using Laser-SNMS and ToF-SIMS. Laser-SNMS studies of pure sirolimus and probucol were undertaken using 30 keV Bi₃⁺ primary Ions and a 157 nm excimer postionization laser. Under optimal conditions, a greater than 100-fold increase in detected ion yield was observed for Laser-SNMS when compared to ToF-SIMS, although ToF-SIMS provided equal or greater yields for higher mass characteristic ions. Although the optimal laser power density for detecting probucol (5x10⁶W/cm²) was significantly lower than the optimum for sirolimus(7x10⁷W/cm²), an intermediate laser power density of 1x10⁷W/cm² was sufficient to allow imaging of both drugs. Using individual selected ion signals, ToF-SIMS and Laser-SNMS produced similar images of the two drug species. When using, however, a multivariate approach (Maximum autocorrelation factors), Laser-SNMS provided significant improvements in image contrast and small area detection when compared to ToF-SIMS.&#13;
Following optimization of the technique, 3D-images of the dual drug eluting stent coating were obtained using 10 keV Ar₂₀₀₀⁺ cluster ions for sputtering and 30 keV Bi₃⁺ cluster ions for Analysis for both ToF-SIMS and Laser-SNMS. This work demonstrates the advantages of Laser-SNMS for 3D-imaging of pharmaceutical devices, which has not been previously published. Both ToF-SIMS and Laser-SNMS revealed that the outermost surface of the drug eluting coating contained pure sirolimus to a depth of a few tens of nanometers, with a few channels of sirolimus extending to a depth of around 1 lm. Below about 1 lm, the two drugs were uniformly mixed. Using the 10 keV Ar₂₀₀₀⁺ sputter beam, the authors were able to sputter through the complete drug coating (~6 μm) without observing any accumulated damage in the organic layer. The two techniques showed complementary strengths: ToF-SIMS offers faster data collection and better detected ion yield for larger characteristic ions than Laser-SNMS, and Laser-SNMS offers significantly enhanced detected ion yield for smaller fragment ions, allowing for improved Image contrast and Resolution of smaller features.</abstract>
    <parentTitle language="eng">Biointerphases</parentTitle>
    <identifier type="doi">10.1116/1.4964687</identifier>
    <identifier type="issn">1934-8630</identifier>
    <identifier type="issn">1559-4106</identifier>
    <enrichment key="date_peer_review">23.02.2017</enrichment>
    <author>Wolfgang Unger</author>
    <author>A. Pelster</author>
    <author>B.J. Tyler</author>
    <author>M. Kösgen</author>
    <author>R. Kassenböhmer</author>
    <author>R.E. Peterson</author>
    <author>M. Stöver</author>
    <author>H. F. Arlinghaus</author>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>Imaging ToF SIMS</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>Eluting stent</value>
    </subject>
    <collection role="ddc" number="543">Analytische Chemie</collection>
    <collection role="literaturgattung" number="">Verlagsliteratur</collection>
    <collection role="fulltextaccess" number="">Datei im Netzwerk der BAM verfügbar ("Closed Access")</collection>
  </doc>
</export-example>
