A point-of-care microfluidic channel-based device for rapid and direct detection of fibrinogen in whole blood

Abstract

Hemorrhage is the leading cause of preventable death in civilian and battlefield traumatic injuries. Patients with severe traumatic hemorrhagic shock are more likely to be deficient in fibrinogen than those with other coagulation factors, and hypofibrinogenemia is an independent risk factor for mortality. Thus, rapid detection of fibrinogen levels is of great importance in these patients during damage control resuscitation. Plasma is used as an analyte in fibrinogen detection, which restricts the use of existing devices in emergencies. To meet the needs of on-site detection, we developed a point-of-care microfluidic channel-based device for direct measurement of fibrinogen concentration in whole blood. In our method, thrombin is dispersed on a reaction strip to initiate conversion of fibrinogen to fibrin. The permeability of the resulting blood clots depends on the fibrinogen level. A hydrophobic plastic protection flake between the reaction strip and a wicking strip is then removed to allow flow of unclotted blood. The rate of blood flow along the wicking strip was inversely related to the fibrinogen concentration. The whole process could be completed in as fast as 5 minutes for a whole blood sample size of 150 μL, and yielded accurate results ranging from 0 to 4 g L⁻¹, which were unaffected by Ca²⁺, blood lipids, hematocrit, warfarin and tissue plasminogen activators (tPAs). Results using clinical whole blood samples were also highly consistent with those using an automatic coagulation analyzer, yielding a Pearson correlation coefficient of up to 0.919. This approach has potential for allowing rapid diagnosis of fibrinogen concentration in critically ill bleeding patients in different settings, thus helping to judge the suitability of fibrinogen replacement therapy (FRT) in cases of emergency bleeding and in patients at risk of thrombosis due to hyperfibrinogenemia.