Coagulation and Platelet Sensing

Photograph of the hand-held sensor, compatible with a Window surface tablet for real-time coagulation profiling in (A) with the corresponding CAD diagram of the optical and mechanical device configuration. The sensor uses a diode laser (DL) to illuminate the sample and a high-speed camera CMOS camera to collect speckle patterns during coagulation. Inexpensive test cartridges are fabricated by laser cutting a silicone base with a transparent film overlay to sample a drop of whole blood.
Photograph of the hand-held sensor, compatible with a Window surface tablet for real-time coagulation profiling in (A) with the corresponding CAD diagram of the optical and mechanical device configuration. The sensor uses a diode laser (DL) to illuminate the sample and a high-speed camera CMOS camera to collect speckle patterns during coagulation. Inexpensive test cartridges are fabricated by laser cutting a silicone base with a transparent film overlay to sample a drop of whole blood.
Laser speckle aggreogometry (LSA) for mapping the platelet aggregation and aggregate size in a small volume of plasma. (a-c) display the map of aggregate sizes (in relative arbitrary units) for a plasma specimen with no ADP added. Similarly, (d-f) display the map of aggregate sizes for a plasma specimen, spiked with a final ADP concentration of 10 μM. These figures illustrate the rapid aggregation of platelets within minutes of ADP activation.
Laser speckle aggreogometry (LSA) for mapping the platelet aggregation and aggregate size in a small volume of plasma. (a-c) display the map of aggregate sizes (in relative arbitrary units) for a plasma specimen with no ADP added. Similarly, (d-f) display the map of aggregate sizes for a plasma specimen, spiked with a final ADP concentration of 10 μM. These figures illustrate the rapid aggregation of platelets within minutes of ADP activation.
Coagulation Curve and Colormap
Coagulation Curve and Colormap
Laser speckle patterns and the corresponding changes in clot stiffness are measured in three patients with normal, low, and high fibrinogen. The capability to form stable fibrin clots depends in part on the amount of fibrinogen, a soluble protein in plasma. Therefore, low levels of fibrinogen impair clot stiffness and is potentially a risk factor for severe bleeding. In contrast, patients with high serum fibrinogen have stiffer clots, that likely contribute to thrombotic events.
Laser speckle patterns and the corresponding changes in clot stiffness are measured in three patients with normal, low, and high fibrinogen. The capability to form stable fibrin clots depends in part on the amount of fibrinogen, a soluble protein in plasma. Therefore, low levels of fibrinogen impair clot stiffness and is potentially a risk factor for severe bleeding. In contrast, patients with high serum fibrinogen have stiffer clots, that likely contribute to thrombotic events.

Our laboratory has developed a low-cost, multi-functional blood coagulation sensor that can measure a patient's coagulation status within minutes using just one drop of blood. This hand-held sensor can identify and manage patients with a high risk of life-threatening bleeding or hemorrhage, which is one of the major causes of preventable in-hospital deaths. It also allows for rapid coagulation testing in the home or primary care setting for over 15 million patients worldwide who receive oral anticoagulants to prevent thrombosis, the leading cause of death worldwide. Our coagulation sensor combines the strengths of a low-cost, hand-held module with the ability to diagnose the underlying coagulation defect within a fraction of the time and cost of conventional coagulation tests. Our approach, Optical Thromboelastography (OTEG) or iCoagLAB, uses a disposable cartridge and laser speckle intensity fluctuations to analyze blood viscoelastic properties during coagulation and recover information about multiple coagulation metrics. OTEG's comprehensive coagulation profiling capabilities at the bedside can improve patient outcomes by identifying high-risk patients, tailoring blood transfusion and anti-coagulation protocols, and monitoring hemostasis during therapy.

Running coagulation experiment via iCoagLAB

Microfluidics

Our laboratory has tackled a common challenge in clinical blood coagulation testing: efficiently mixing blood, a shear-thinning fluid, with reagents at the fast speed required for accurate blood coagulation testing. We have developed a novel approach that utilizes 3D passive helicoidal mixers within the cartridge to enhance mixing efficiency. Our mixer designs have been rigorously tested through flow simulations, dye mixing, and blood coagulation experiments to ensure optimal performance. The resulting iCoagLAB device-compatible cartridge comprises a reagent chamber, a passive mixer, an optical testing chamber, and a vent, all of which work together to facilitate successful blood coagulation experiments monitored through laser speckle rheology technology. Moving forward, we aim to collaborate with industrial partners to employ high-precision fabrication methods for mass-producing these cartridges. 

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Optimizing mixer design via fluid simulation Comparing blood mixing at cartridges with different passive mixers
Optimizing mixer design via fluid simulation Comparing blood mixing at cartridges with different passive mixers

Running coagulation experiment via iCoagLAB

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