title: A portable blood plasma clot micro-elastometry device based on resonant acoustic spectroscopy.
abstract: Abnormal blood clot stiffness is an important indicator of coagulation disorders arising from a variety of cardiovascular diseases and drug treatments. Here, we present a portable instrument for elastometry of microliter volume blood samples based upon the principle of resonant acoustic spectroscopy, where a sample of well-defined dimensions exhibits a fundamental longitudinal resonance mode proportional to the square root of the Young's modulus. In contrast to commercial thromboelastography, the resonant acoustic method offers improved repeatability and accuracy due to the high signal-to-noise ratio of the resonant vibration. We review the measurement principles and the design of a magnetically actuated microbead force transducer applying between 23 pN and 6.7 nN, providing a wide dynamic range of elastic moduli (3 Pa-27 kPa) appropriate for measurement of clot elastic modulus (CEM). An automated and portable device, the CEMport, is introduced and implemented using a 2 nm resolution displacement sensor with demonstrated accuracy and precision of 3% and 2%, respectively, of CEM in biogels. Importantly, the small strains (<0.13%) and low strain rates (<1/s) employed by the CEMport maintain a linear stress-to-strain relationship which provides a perturbative measurement of the Young's modulus. Measurements of blood plasma CEM versus heparin concentration show that CEMport is sensitive to heparin levels below 0.050 U/ml, which suggests future applications in sensing heparin levels of post-surgical cardiopulmonary bypass patients. The portability, high accuracy, and high precision of this device enable new clinical and animal studies for associating CEM with blood coagulation disorders, potentially leading to improved diagnostics and therapeutic monitoring.
authors.affiliation: Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Krebs
authors.affiliation: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Alisa S
authors.initials: AS
authors.lastname: Wolberg
authors.affiliation: Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Oldenburg
mesh_terms: D000162:Acoustics / Q000295:instrumentation*; D000925:Anticoagulants / Q000494:pharmacology; D057205:Automation, Laboratory / Q000295:instrumentation; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001780:Blood Coagulation Tests / Q000295:instrumentation*; D002138:Calibration; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D055119:Elastic Modulus; D004867:Equipment Design; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D016014:Linear Models; D059346:Magnets; D008863:Microspheres; D055616:Microtechnology / Q000295:instrumentation*; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio; D013057:Spectrum Analysis / Q000295:instrumentation*; D014732:Vibration
chemical_list: D000925:Anticoagulants; D006493:Heparin