OC 15.5 - Detection of TIC-relevant Phenotypes Using Bioactive Reagent-functionalized Dielectric Coagulometry Microsensors

Background: Trauma-induced coagulopathy (TIC) is the dysregulation of hemostatic mechanisms involving platelets, coagulation factors, and the fibrinolytic system following traumatic injury and is a major cause of mortality. Management of TIC relies on thromboelastometry or thromboelastography devices to guide resuscitation. However, these devices pose challenges for point-of-care/point-of-injury (POC/POI) use due to their high cost, large size, and limited portability. We hypothesized that dielectric spectroscopy (DS)-based microsensors coated with reagents capable of modulating hemostatic responses could enable detection of TIC-relevant phenotypes in a portable platform suitable for POC/POI applications (Fig. 1A).

Aims: We aimed to evaluate TIC-relevant hemostatic dysfunctions using surface-coated DS-based microsensors.

Methods: DS microsensors were fabricated from gold electrode-bearing polymethyl methacrylate (PMMA) parts held together by double-sided adhesive (DSA, 1B). The electrodes were either uncoated or coated with thrombin receptor activating peptide 6 (TRAP-6), tissue factor (TF), or aprotinin to respectively probe platelet, coagulation, or fibrinolytic function (1C). Sensors were used in DS experiments to characterize the hemostatic profile of healthy whole blood (HWB) or blood with a TIC-relevant defect, enabling quantification of clotting time and lysis time.

Results: The clotting time of HWB on TRAP-6-coated microsensors was reduced by 40% relative to uncoated sensors. In contrast, the clotting profile of blood with a platelet defect was not sensitive to TRAP-6, providing a diagnostic signature (Fig. 2A). Similarly, clotting kinetics were accelerated two-fold on TF-coated electrodes for HWB, but not affected by TF for blood with a coagulation factor VII deficiency (2B). Clots formed from HWB did not undergo fibrinolysis on uncoated electrodes; however, clots formed from blood with induced hyperfibrinolysis exhibited lysis within 20 min. The aprotinin-modified electrode rescued the HWB lytic profile (2C).

Conclusion(s): We have developed a DS-based miniaturized platform for detecting TIC-relevant phenotype-specific signatures sensitive to platelet, coagulation, and fibrinolytic function, which could potentially guide resuscitative transfusion approaches.