Hemostatic monitoring presents critical importance in situations of breakthrough bleeding, ongoing surgery, and development of anticoagulant therapies. In the final paper, we will describe a functional microfluidic system integrated with a micro particle image velocimetry (PIV) technique for rapid and rheological assessment of whole blood coagulation. Wavelet-based optical flow velocimetry (wOFV) is then used to more precisely analyze blood flow dynamics during coagulation. The system allows monitoring and quantifying coagulation dynamics under physiologic flow conditions that can be adjusted to mimic arterial or venous shear rates. Further, this microfluidic platform holds a potential to interrogate the effect of various activators or inhibitors (e.g. collagen, tissue factor, heparin, etc.) on blood coagulometric dynamics via covalent immobilization of these agents on the microchannel surface. The microfluidic devices consist of a laser micro-machined polymethyl methacrylate (PMMA) cover, double-sided adhesive film (DSA), and standard microscope glass slide, yielding a microchannel width and height of 4 mm and 50 μm respectively. The blood samples obtained in sodium citrate vacutainers were re-calcified in 250 mM CaCl~2~ and injected into a microchannel under a constant pressure of 20 mBar. The microfluidic devices were placed on an inverted microscope, and the fluid flow was recorded at 4X magnification for 9 minutes followed by a PIV analysis to obtain mean velocity values on a given field of view. Since the mean velocity is a function of blood viscosity, which dramatically changes during coagulation, a dramatic drop in mean blood velocity was regarded as the initiation of sample coagulation time. The blood is not seeded with foreign particles for velocity analysis; the red blood cells themselves serve as flow markers.

More importantly, characterization of distorted blood flow around the thrombi that form following the onset of coagulation cascade may provide additional insights into the blood clotting profiles of clinically diverse patient populations with potential coagulation disorders. This may have further patient-specific implications in functionalized microfluidic channels to probe the effect of individual or multiple factors in the coagulation profile (e.g. factor XII, factor VIII, etc.). State-of-the-art correlation-based PIV processing is unable to provide this more detailed information about the blood flow during coagulation due to inherent limitations in spatial resolution. PIV processing is also known to be less accurate for natural (i.e., unseeded) images like the ones in the present study. wOFV does not suffer the same limitations and is able to provide accurate, highly spatially resolved information about the complex flow patterns which form during coagulation. Preliminary results from wOFV processing demonstrate the resolution of multiple flow channels around thrombi. In the final paper, these data will be analyzed to determine the flow rates through these channels as well as their temporal evolution throughout the coagulation process.


Blood Flow Velocimetry in a Microchannel During Coagulation Using PIV and wOFV

Division / Sponsors: 
Aerospace, Bioengineering, Applied Mechanics, Design Engineering Division, Advanced Energy Systems, Manufacturing Engineering Division, Noise Control and Acoustics, Nondestructive Evaluation, Diagnosis, and Prognosis (NDPD), Nuclear Engineering Division, Process Industries Division, Fluids Engineering, Heat Transfer, Materials, Microelectromechanical Systems, Safety Engineering and Risk Analysis, Computers & Information in Engineering


Paper Proceedings: https://asmedigitalcollection.asme.org/IMECE/IMECE2020/volume/84478

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