A multi-readout photonic sensor for rapid diagnosis of Von Willebrand disease

Von Willebrand Disease (VWD) is characterized by improper blood clotting, resulting from qualitative or quantitative changes in Von Willebrand factor (VWF). Diagnosis of VWD currently relies on measuring both the concentration of VWF and its activity by the binding ability to several different proteins, each of which are currently quantified separately. As such, the current diagnosis of VWD is complex and expensive, requiring multiple tests for a positive clinical determination. To address this challenge, we report a multiplexed biosensor that simultaneously measures VWF concentration and binding activity in plasma, enabling rapid diagnosis of VWD and discrimination among multiple subtypes. Using an 18-plex photonic ring resonator in a disposable, lateral flow assay-like format as the core technology, capture of VWF by an immobilized monoclonal antibody results in a red shift in resonance, which is referenced to a nonspecific binding control. Other ring resonators on the chip, functionalized with binding partners of VWF, allow simultaneous measurement of VWF binding to collagen, Factor VIII, and the GP1b receptor. Evaluation of a panel of 37 single-donor human plasma samples previously analyzed using FDA clinically approved assays demonstrated that the sensor has comparable concentration results and was able to accurately identify several categories of VWD (type 1, 2 A, and type 3).