dynamic-multiparameter-platelet-function-assessment-using-capacitive

Dynamic Multiparameter Platelet Function Assessment Using a Capacitive Biosensor

Platelets play a fundamental role in blood clotting through a series of regulated responses, including adhesion, spreading, granular secretion, ...

University of Washington

Rapid and uniform rewarming has been proved to be beneficial, and sometimes indispensable for the survival of cryopreserved biomaterials, inhibiting ice-recrystallization-devitrification and thermal stress-induced fracture (especially in large samples). To date, the convective water bath remains the gold standard rewarming method for small samples in the clinical settings, but it failed in the large samples (e.g., cryopreserved tissues and organs) due to damage caused by the slow and nonuniform heating. A single-mode electromagnetic resonance (SMER) system was developed to achieve ultrafast and uniform rewarming for large samples. In this study, we investigated the heating effects of the SMER system and compared the heating performance with water bath and air warming. A numerical model was established to further analyze the temperature change and distribution at different time points during the rewarming process. Overall, the SMER system achieved rapid heating at 331.63 ± 8.59°C min while limiting the maximum thermal gradient to <9°C min, significantly better than the other two warming methods. The experimental results were highly consistent, indicating SMER is a promising rewarming technology for the successful cryopreservation of large biosamples.

Single-Mode Electromagnetic Resonance Rewarming for the Cryopreservation of Samples with Large Volumes: A Numerical and Experimental Study.

Long-term cryopreservation of human umbilical vein endothelial cells (HUVECs) is important and beneficial for a variety of biomedical research and applications. In this study, we investigated HUVEC's cryobiological characteristics and parameters that are indispensable for predicting and determining an optimal cooling rate to prevent lethal intracellular ice formation (IIF) and severe cell dehydration during the cryopreservation processes. The parameters include cell membrane hydraulic conductivity (i.e., cell membrane water permeability), , cell membrane water permeability activation energy, , and osmotically inactive volume of a cell . Cryomicroscopy was used to study the IIF phenomena and cell volume excursion at various cooling rates, 1, 10, and 20°C/min, respectively, based on which the cryobiological parameters were determined using biophysical and mathematical models. Results from this research work laid an important cryobiological foundation for the optimization of HUVEC's cryopreservation conditions.

Transmembrane Water Transport and Intracellular Ice Formation of Human Umbilical Vein Endothelial Cells During Freezing.

Background: Residual viable tumor cells after ablation at the tumor periphery serve as the source for tumor recurrence, leading to treatment failure. Purpose: To develop a novel three-dimensional (3D) multi-modal perfusion-thermal electrode system completely eradicating medium-to-large malignancies. Materials and Methods: This study included five steps: (i) design of the new system; (ii) production of the new system; (iii) ex vivo evaluation of its perfusion-thermal functions; (iv) mathematic modeling and computer simulation to confirm the optimal temperature profiles during the thermal ablation process, and; (v) in vivo technical validation using five living rabbits with orthotopic liver tumors. Results: In ex vivo experiments, gross pathology and optical imaging demonstrated the successful spherical distribution/deposition of motexafin gadolinium administered through the new electrode, with a temperature gradient from the electrode core at 80 °C to its periphery at 42 °C. An excellent repeatable correlation of temperature profiles at varying spots, from the center to periphery of the liver tumor, was found between the mathematic simulation and actual animal tumor models (Pearson coefficient ≥0.977). For in vivo validation, indocyanine green (ICG) was directly delivered into the peritumoral zones during simultaneous generation of central tumoral lethal radiofrequency (RF) heat (>60 °C) and peritumoral sublethal RF hyperthermia (<60 °C). Both optical imaging and fluorescent microscopy confirmed successful peritumoral ICG distribution/deposition with increased heat shock protein 70 expression. Conclusion: This new 3D, perfusion-thermal electrode system provided the evidence on the potential to enable simultaneous delivery of therapeutic agents and RF hyperthermia into the difficult-to-treat peritumoral zones, creating a new strategy to address the critical limitation, i.e., the high incidence of residual and recurrent tumor following thermal ablation of unresectable medium-to-large and irregular tumors.

Development of a Three-Dimensional Multi-Modal Perfusion-Thermal Electrode System for Complete Tumor Eradication.

When stimulated by proinflammatory mediators, endothelial cells release ultra-large von Willebrand factor (ULVWF) multimers that are hyperactive in activating and aggregating platelets. These ULVWF multimers can accumulate in the circulation and on the inflamed endothelium because they are insufficiently cleaved by the metalloprotease ADAMTS-13, which becomes moderately deficient under conditions of systemic inflammation. This moderate ADAMTS-13 deficiency may lead to thrombotic complications that contribute to ischemic tissue injury and organ failure that are associated with severe infections. To test this hypothesis, we investigated whether recombinant ADAMTS-13 improves the pathological course of endotoxemia in lipopolysaccharide (LPS)-treated mice. C57BL/J6 mice received a bolus infusion of either 5 µg/mouse of ADAMTS-13 or vehicle control 30 min after LPS challenge and were monitored for seven-day survival. During the monitoring period, platelet counts, VWF antigen, and ADAMTS-13 activity were measured. Thrombosis was also examined by the immunohistochemistry in the liver. We found that ADAMTS-13 reduced mortality from 66% to 34.9%. The improved survival was associated with a greater recovery from thrombocytopenia, higher plasma ADAMTS-13 activity, and less thrombotic vascular occlusion. These results suggest that systemic inflammation could result in deficient ULVWF proteolysis by ADAMTS-13 and that ADAMTS-13 improves the outcomes of endotoxemia-induced inflammation.

Ruidong Ma

Department of Mechanical Engineering

University of Washington

Dynamic Multiparameter Platelet Function Assessment Using a Capacitive Biosensor

Ruidong Ma

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Mechanical Engineering

University of Washington

Dynamic Multiparameter Platelet Function Assessment Using a Capacitive Biosensor

Department of Mechanical Engineering