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CORE COMPETENCY: CLINCIAL ASSAYS OF PLATELET FUNCTION
  • RESEARCH OVERVIEW
  • KEY OUTPUTS
  • PRINCIPAL INVESTIGATOR
RESEARCH OVERVIEW:

Cardiovascular disease is the largest cause of global mortality. This is frequently due to thrombosis mediated by platelets. Current assays to initiate therapy in either primary or secondary prevention of thrombosis have significant limitations. Moreover, assays of platelet function as a risk marker for cardiovascular events are not routine. The platelet biology research program involves the development of novel diagnostic microfluidic & adhesion assay devices for assessment of platelet function in cardiovascular disease, bleeding disorders, and other afflictions, all under conditions found in the vascular system.

To date we have extensively demonstrated two categories of assay, including proof of function of the devices in clinical testing. One is a novel platelet-adhesion assay that reliably quantifies the effect of antiplatelet agents in patients with cardiovascular disease. The second is an integrated microfluidic flow device that assays a few drops of blood to measure the statistics of dynamic interactions between platelets under arterial rates of shear stress with surface-immobilized proteins found within the vascular system. This so-called Dynamic Platelet Function Assay (DPFA) provides new insights and diagnostic information on platelet function relevant to cardiovascular disease, bleeding disorders, and a range of other diseases that impact normal platelet function.

Key programme elements:

  • Clinical testing on hundreds of healthy donors and patients of a dynamic platelet function assay microfluidic device that assesses platelet function in terms of platelet-protein interactions in normal and diseased patient cohorts
  • Clinical testing of a novel single-platelet adhesion device for drug effect in vivo
  • Application of these assay devices for the characterisation and assessment of platelet function and reactivity in cardiovascular disease and bleeding disorders
  • Development of both assays and the associated measurement systems for pre-commercial assessment in the clinical context

KEY OUTPUTS:
SELECTED PUBLICATIONS:
  • Jose B, McCluskey P, Gilmartin N, Somers M, Kenny D, Ricco AJ, Kent NJ, Basabe-Desmonts L. Self-Powered Microfluidic Device for Rapid Assay of Antiplatelet Drugs. Langmuir. 2016:32;2820-8.

  • Cowman J, Quinn N, Geoghegan S, Müllers S, Oglesby I, Byrne B, Somers M, Ralph A, Voisin B, Ricco AJ, Molloy EJ. Dynamic platelet function on von Willebrand factor is different in preterm neonates and full‐term neonates: changes in neonatal platelet function. Journal of Thrombosis and Haemostasis. 2016:14;1-9.

  • Cowman J, Dunne E, Oglesby I, Byrne B, Ralph A, Voisin B, Müllers S, Ricco AJ, Kenny D. Age-related changes in platelet function are more profound in women than in men. Scientific reports. 2015:5;12235.

  • Fitzgibbon S, Cowman J, Ricco AJ, Kenny D, Shaqfeh ES. Examining platelet adhesion via Stokes flow simulations and microfluidic experiments. Soft matter. 2015:11;355-67.

  • Lopez-Alonso A, Jose B, Somers M, Egan K, Joley DP, Ricco AJ, Ramstrom S, Basabe-Desmonts L, Kenny D. (2013) Individual Platelet Adhesion (iPA) Assay: Measuring Platelet Function and Anti-Platelet Therapies in Whole Blood via Digital Quantification of Cell Adhesion. Analytical Chemistry.

  • Lucitt MB, O'Brien S, Cowman J, Meade G, Basabe-Desmonts L, Somers M, Kent N, Ricco AJ, Kenny D. (2013) 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. Analytical and Bioanalytical Chemistry. (Mar)

  • Woolley R, Prendergast Ú, Jose B, Kenny D, McDonagh C. A rapid, topographical platelet activation assay. Analyst. 2013:138;4512-8.

  • O'Brien S, Kent NJ, Lucitt M, Ricco AJ, McAtamney C, Kenny D, Meade G. (2012) Effective hydrodynamic shaping of sample streams in a microfluidic parallel-plate flow-assay device: matching whole blood dynamic viscosity. IEEE Trans Miomed Eng. (Feb) 59(2):374-82.

  • Bernard E, Buckley V, Moman E, Coleman L, Meade G, Kenny D, Devocelle M. Inhibition of Platelet Adhesion by Peptidomimetics Disrupting GPIbα-vWF Interaction. In Press Bioorganic & Medicinal Chemistry Letters. 2012:22;3323-6

  • Woolley R, Roy S, Prendergast Ú, Basabe-Desmont L, Kenny D, McDonagh. From particle to platelet: optimization of a stable, high brightness fluorescent nanoparticle based cell detection platform. Nanomedicine. 2012.12;596-5

  • Egan K, Crowley D, Smyth P, O'Toole S, Spillane C, Martin C, Gallagher M, Canney A, Norris L, Conlon N, McEvoy L, Ffrench B, Stordal B, Keegan H, Finn S, Ducree J, Dunne E, Smith L, Berndt MC, Sheils O, Kenny D, O'Leary JJ. Platelet adhesion and degranulation induce pro-survival and pro- angiogenic signalling in ovarian cancer cells. PLoS One. 2011:6;e26125.

  • Kent NJ, O'Brien S, Basabe-Desmonts L, Meade GR, MacCraith BD, Corcoran BG, Kenny D, Ricco AJ. Shear-Mediated Platelet Adhesion Analysis in Less Than 100 µl of Blood: Toward a POC Platelet Diagnostic. IEEE Trans Biomed Eng. 2011:58;826-30.

  • Ramstrom S., O'Neill S., Kenny D. Annexin V binding to platelets is agonist, time, and temperature dependant, Platelets. 2010;21:289-96

  • Lincoln B, Ricco AJ, Kent NJ, Basabe-Desmonts L, Lee LP, MacCraith BD, Kenny D, Meade GR. Integrated system investigating shear-mediated platelet interactions with von Willebrand factor using microlitre volumes of whole blood. Analytical Biochemistry. 2010;405:174-83

  • Basabe-Desmonts,L, Ramstrom S, Meade G, O'Neill S, Riaz A, Lee LP, Ricco AJ, Kenny D. Single-step separation of platelets from whole blood coupled with digital quantification by interfacial platelet cytometry. Langmuir 2010;21:174-83

  • Kent NJ, Basabe-Desmonts L, Meade GR, Corcoran BG, Kenny D, Ricco AJ. Microfluidic Device to study shear-mediated platelet-surface interactions in whole blood: reduced sample volumes and well-characterized protein surfaces. Biomedical Microdevices. 2010 Dec;12(6):987-1000

INTELLECTUAL PROPERTY:

  • Intellectual Property information is available here.

 

 

 

CLINICAL LEAD:
Dermot Kenny MD, FACC, FRCPI, DABIM (cardiovascular disease)

Professor Cardiovascular Biology / Director of the Clinical Research Centre, Royal College of Surgeons in Ireland; Adjunct Professor, Dublin City University.

Dermot Kenny graduated from the Royal College of Surgeons in Ireland in 1982. He completed his training in Internal Medicine in Dublin and moved to the USA in 1987 where he completed his cardiology fellowship and started his research career in coronary physiology and thrombosis. The NIH, American Heart Association, Wellcome Trust and more recently the Health Research Board in Ireland have funded his research.

In 1998 he returned to Dublin to head up the first academic clinical research centre in Ireland. Professor Kenny maintains an active research role as an Investigator in the Blood Research Institute of the Blood Center of Southeastern Wisconsin He is adjunct Associate Professor of Cardiovascular Medicine in the Medical College of Wisconsin and Adjunct Professor in the Biomedical Diagnostics Institute in Dublin City University.

His primary research area is in understanding the mechanisms of thrombosis to advance clinical diagnostics. His contributions to translational research have recently been recognised in a number of awards by the Royal College of Surgeons in Ireland. His personal interests includes scuba diving, both ice diving and in the more temperate waters of Ireland.

ACADEMIC LEAD:
Prof. Antonio Ricco PhD.

Adjunct Professor, School of Biotechnology, Dublin City University Chief Technologist, Small Payloads, NASA Ames Research Center (on assignment from Stanford University)

Antonio J. Ricco is Chief Technologist for Small Payloads at NASA's Ames Research Center, on assignment from Stanford University, and he is Adjunct Professor in the School of Biotechnology in Dublin, Ireland. Ricco received BS and PhD degrees in Chemistry from the University of California at Berkeley and the Massachusetts Institute of Technology, respectively. He developed chemical microsensor technologies and systems at Sandia National Laboratories from 1984 to 1998 and was guest professor for a semester at the University of Heidelberg's Applied Physical Chemistry Institute in 1996. From 1999 to 2003 at ACLARA BioSciences, he led development of single-use plastic microfluidic systems for genetic analysis, high-throughput pharmaceutical discovery, proteomics, and pathogen detection. He was Director of Stanford's National Center for Space Biological Technologies from 2004 to 2007; since 2007, he has been at NASA's Ames Research Center, on assignment from Stanford. From 2003 to 2015, he was involved in the founding, planning, growth, and projects of the Biomedical Diagnostics Institute, including participation in many of the BDI’s research, development, and clinical application projects.