NguyenVizcarra_CapstoneResearchSymposiumSlides
- 1. Point-of-Care Fibrinogen Monitor for TIC Team Members: Albert Nguyen & Juan Vizcarra Mentor: Dr. Nathan White (Emergency Medicine, Harborview)
- 2. Background • Trauma: sudden and severe injury that requires immediate medical attention • Leading cause of death for the young population in the world • Primary cause: uncontrolled bleeding • Trauma-Induced Coagulopathy (TIC): Impaired ability to form a healthy blood clot due to heavy blood loss from trauma • 4-fold increase in mortality when present
- 3. Background Consequences of Misdiagnosis Coagulopathy Diagnosis False - False + ● Standard rescucitation fluids administered ● Patient bleeds to death ● Coagulants administered ● Induced hypercoagulation leads to strokes or thrombosis
- 4. Clinical Need • Role of Fibrinogen • releases fibrin monomers which leads to scaffold of clot • depletes first during trauma • shown to be strong indicator of coagulopathy • Current Limitations • Devices are too big, slow, and thus inaccessible for urgent trauma patients • Need • A point-of-care device that can access the quality of a clot quickly, reliably, and in a portable manner
- 5. Previous Design • 1: Solenoid • 2: LVDT • 3: Cuvette with spring • 4: Cuvette dark chamber • Measured turbidity of sample and the total displacement by solenoid
- 6. Previous Design Results and Limitation • Hemostatic Ratio: Ratio between turbidity and solenoid displacement • Limitations: • Good PPP results, bad whole blood results • Poor correlation between ratio and concentration
- 7. Our New Approach Porosity Measurement • Replaced turbidity measurement • Gives information on structure Stiffness Measurement • Cantilever-based approach to increase mechanical measurement sensitivity SEM Images of Fibrin Hydrogels
- 8. Porosity Approach • Pore size measurement based on Darcy’s Law • 𝐷𝑎𝑟𝑐𝑦′ 𝑠 𝐿𝑎𝑤: 𝑄 = −𝑘𝐴 𝑝 𝑏 − 𝑝 𝑎 µ𝐿 • 𝑃𝑜𝑟𝑒 𝑠𝑖𝑧𝑒 = 0.5093 ∗ 𝑘 • Calculated after certain amount of buffer permeates through clot • Intend to add fluid pump/sensor to regulate and measure pressure Weigandt et al. Biophysical Journal 103.11 (2012): 2399-407. Web.
- 9. Porosity Apparatus • Formed clots in etched polystyrene tubes • Attached tubes to water bags and determined permeation time for 0.5-1.5 mL of water • Performed tests on: • Pure Fibrinogen Solution • Diluted human blood • Whole human blood
- 10. Porosity Results • Lower concentrations gave inaccurate results • Whole blood unable to stick to tube and maintain structure • St. Dev shown • n = 3 for each data point
- 11. Cantilever Approach • Motion driven by solenoid • Custom designed silicone cantilevers for increased sensitivity • Segmented Photodiode for detection • Force-displacement measurements to approximate tensile modulus D𝑒𝑓𝑙𝑒𝑐𝑡𝑖𝑜𝑛 = 𝐼𝑛𝑣𝑂𝐿𝑆 ∗ ∆𝑉𝑜𝑙𝑡𝑎𝑔𝑒 𝐹𝑜𝑟𝑐𝑒 = 𝑘 𝑐𝑎𝑛𝑡𝑖𝑙𝑒𝑣𝑒𝑟 ∗ 𝐷𝑒𝑓𝑙𝑒𝑐𝑡𝑖𝑜𝑛 A B C D 𝐷𝑒𝑓𝑙𝑒𝑐𝑡𝑖𝑜𝑛 = 𝑉𝐴 + 𝑉𝐵 − (𝑉𝐶 + 𝑉𝐷)
- 12. Cantilever Design Overview • MOSFET Switch circuit & LABVIEW used to control cantilever movement • LABVIEW used for analysis of signals through DAQ device
- 13. 1) Segmented Photodiode 2) Laser Pen 3) Cantilever Holder 4) Cantilever (Aluminum Coating) 5) MOSFET Switch Circuit 6) DAQ 7) 24V Solenoid
- 14. Cantilever Design Images No light Ambient Light Laser Light Voltage(V)
- 15. Cantilever Design • Current State: Able to take flat surface measurements • Next Steps: • Laser light focusing needed • Cantilever geometry redesign • Increase reflectivity of signal
- 16. Future Work • Incorporate size-exclusion filter to remove RBCs • Add miniature pressure pump to better control permeation • Modify conditions to minimize permeation time • Test cantilever design on blood clots • Assess correlation of hemostatic ratio for our tests to fibrinogen concentration
Editor's Notes
- #2: Juan
- #3: Juan Young usually healthy; young and healthy associated with poor decision making
- #4: Juan
- #5: Juan
- #6: Juan
- #7: Albert Turbidity cannot be measured on whole blood
- #8: Albert New hemostatic ratio to potentially improve correlation and be able to use whole blood Even if same pore size, may have different mechanical properties
- #9: Albert
- #10: Albert
- #11: Albert Physiologic range around 2.2 mg/mL Data points thus far show strong correlation between pore size and fibrinogen concentration Also tested lower concentrations but flow rate similar to no clot at all, not accurate Unable to test whole blood since clots not strong enough to stick to tube Fibrin network forms around RBCs so clot weakened, supported by larger pore size
- #12: Juan Idea based on AFM technology
- #13: Juan
- #14: Juan
- #15: Juan
- #16: Juan
- #17: Albert Current permeation time upwards of 20 minutes
- #18: Albert