title: Microfluidic emulation of mechanical circulatory support device shear-mediated platelet activation.
abstract: Thrombosis of ventricular assist devices (VADs) compromises their performance, with associated risks of systemic embolization, stroke, pump stop and possible death. Anti-thrombotic (AT) drugs, utilized to limit thrombosis, are largely dosed empirically, with limited testing of their efficacy. Further, such testing, if performed, typically examines efficacy under static conditions, which is not reflective of actual shear-mediated flow. Here we adopted our previously developed Device Thrombogenicity Emulation methodology to design microfluidic platforms able to emulate representative shear stress profiles of mechanical circulatory support (MCS) devices. Our long-term goal is to utilize these systems for point-of-care (POC) personalized testing of AT efficacy under specific, individual shear profiles. First, we designed different types of microfluidic channels able to replicate sample shear stress patterns observed in MCS devices. Second, we explored the flexibility of microfluidic technology in generating dynamic shear stress profiles by modulating the geometrical features of the channels. Finally, we designed microfluidic channel systems able to emulate the shear stress profiles of two commercial VADs. From CFD analyses, the VAD-emulating microfluidic systems were able to replicate the main characteristics of the shear stress waveforms of the macroscale VADs (i.e., shear stress peaks and duration). Our results establish the basis for development of a lab-on-chip POC system able to perform device-specific and patient-specific platelet activation state assays.
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, 20133, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Dimasi
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, 20133, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rasponi
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794-8151, USA.
authors.forename: Jawaad
authors.initials: J
authors.lastname: Sheriff
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794-8151, USA.
authors.forename: Wei-Che
authors.initials: WC
authors.lastname: Chiu
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794-8151, USA.
authors.forename: Danny
authors.initials: D
authors.lastname: Bluestein
authors.affiliation: Department of Medicine and Biomedical Engineering, Sarver Heart Center, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ, 85724, USA.
authors.forename: Phat L
authors.initials: PL
authors.lastname: Tran
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794-8151, USA. chairman.syns@gmail.com.|Department of Medicine and Biomedical Engineering, Sarver Heart Center, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ, 85724, USA. chairman.syns@gmail.com.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Slepian
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, 20133, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Redaelli
mesh_terms: D001792:Blood Platelets / Q000166:cytology*; D019295:Computational Biology; D004867:Equipment Design; D005240:Feasibility Studies; D006353:Heart-Assist Devices; D006801:Humans; D056656:Lab-On-A-Chip Devices; D044085:Microfluidics; D015539:Platelet Activation; D019095:Point-of-Care Systems; D013314:Stress, Mechanical; D013927:Thrombosis / Q000628:therapy
keywords: Anti-thrombotic therapy; Computational fluid dynamics; Mechanical circulatory support; Microfluidics; Thrombosis; Ventricular assist devices