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Analytical and Bioanalytical Chemistry

, Volume 405, Issue 14, pp 4823–4834 | Cite as

Assaying the efficacy of dual-antiplatelet therapy: use of a controlled-shear-rate microfluidic device with a well-defined collagen surface to track dynamic platelet adhesion

  • Margaret B LucittEmail author
  • Sinead O’Brien
  • Jonathan Cowman
  • Gerardene Meade
  • Lourdes Basabe-Desmonts
  • Martin Somers
  • Nigel Kent
  • Antonio J. Ricco
  • Dermot Kenny
Research Paper

Abstract

We report the development and demonstration of an assay that distinguishes the pharmacological effects of two widely used antiplatelet therapies, aspirin (COX-1 inhibitor) and clopidogrel (P2Y12 inhibitor). Whole blood is perfused through a low-volume microfluidic device in contact with a well-characterized (ellipsometry, atomic force microscopy) acid-soluble type I collagen surface. Whole human blood treated in vitro with a P2Y12 inhibitor 2-methylthioadenosine 5′-monophosphate triethylammonium salt (2-MeSAMP) extended the time to the start of platelet recruitment, i.e., platelet binding to the collagen surface. Treatment with 2-MeSAMP also slowed the rate of aggregate buildup, with an overall reduced average platelet aggregate area after 8 min of constant blood flow. A far smaller effect was observed for in vitro treatment with aspirin, for which the rate of change of surface coverage is indistinguishable from controls. In whole blood obtained from patients under treatment with dual-antiplatelet therapy (aspirin and clopidogrel), a significant extension of time to platelet recruitment was observed along with a slowed rate of aggregate buildup and an average aggregate size approximately half that of control measurements. Differentiation of the pharmacological effects of these two well-targeted antiplatelet pathways suggests a role for this assay in determining the antiplatelet effects of these and related new therapeutics in clinical settings.

Keywords Antiplatelet therapy Collagen–platelet interactions Microfluidics Parallel-plate flow chamber Thrombosis 

Notes

Acknowledgments

The authors gratefully acknowledge the help of Ms. Gail Plunkett who assisted with patient recruitment. This material is based upon research supported by Science Foundation Ireland under grant no. 05/CE3/B754.

Disclosure and conflict of interests

The authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Margaret B Lucitt
    • 1
    • 4
    Email author
  • Sinead O’Brien
    • 1
  • Jonathan Cowman
    • 1
  • Gerardene Meade
    • 1
  • Lourdes Basabe-Desmonts
    • 2
    • 3
    • 5
  • Martin Somers
    • 2
  • Nigel Kent
    • 2
    • 6
  • Antonio J. Ricco
    • 2
  • Dermot Kenny
    • 1
    • 2
  1. 1.Biomedical Diagnostics InstituteRoyal College of Surgeons in IrelandDublin 2Ireland
  2. 2.Biomedical Diagnostics InstituteDublin City UniversityDublin 9Ireland
  3. 3.IKERBASQUEBasque Foundation for ScienceBilbaoSpain
  4. 4.Department of Pharmacology and TherapeuticsTrinity College DublinDublin 8Ireland
  5. 5.CIC microGUNEArrasate‐MondragonSpain
  6. 6.Dublin Institute of TechnologyDublin 6Ireland

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