Point-of-Care Fibrinogen Monitor for TIC

Point-of-Care Fibrinogen Monitor for TICTeam Members: Albert Nguyen & Juan VizcarraMentor: Dr. Nathan White (Emergency Medicine, Harborview)

Juan1

BackgroundTrauma: sudden and severe injury that requires immediate medical attentionLeading cause of death for the young population in the worldPrimary cause: uncontrolled bleeding

Trauma-Induced Coagulopathy (TIC): Impaired ability to form a healthy blood clot due to heavy blood loss from trauma4-fold increase in mortality when present

JuanYoung usually healthy; young and healthy associated with poor decision making2

BackgroundConsequences of MisdiagnosisCoagulopathyDiagnosisFalse -False+Standard rescucitation fluids administered

Patient bleeds to deathCoagulants administered

Induced hypercoagulation leads to strokes or thrombosis

Juan3

Clinical NeedRole of Fibrinogenreleases fibrin monomers which leads to scaffold of clotdepletes first during traumashown to be strong indicator of coagulopathy

Current LimitationsDevices are too big, slow, and thus inaccessible for urgent trauma patients

NeedA point-of-care device that can access the quality of a clot quickly, reliably, and in a portable manner

Juan4

Previous Design

1: Solenoid 2: LVDT 3: Cuvette with spring4: Cuvette dark chamber

Measured turbidity of sample and the total displacement by solenoid

Juan5

Previous Design Results and LimitationHemostatic Ratio: Ratio between turbidity and solenoid displacement

Limitations:Good PPP results, bad whole blood resultsPoor correlation between ratio and concentration

AlbertTurbidity cannot be measured on whole blood6

Our New ApproachPorosity MeasurementReplaced turbidity measurementGives information on structure

Stiffness MeasurementCantilever-based approach to increase mechanical measurement sensitivity

SEM Images of Fibrin Hydrogels

AlbertNew hemostatic ratio to potentially improve correlation and be able to use whole bloodEven if same pore size, may have different mechanical properties7

Porosity Approach

Weigandt et al.Biophysical Journal103.11 (2012): 2399-407. Web.

Albert8

Porosity ApparatusFormed clots in etched polystyrene tubesAttached tubes to water bags and determined permeation time for 0.5-1.5 mL of waterPerformed tests on:Pure Fibrinogen SolutionDiluted human bloodWhole human blood

Albert9

Porosity Results

Lower concentrations gave inaccurate results

Whole blood unable to stick to tube and maintain structure

St. Dev shownn = 3 for each data point

AlbertPhysiologic range around 2.2 mg/mLData points thus far show strong correlation between pore size and fibrinogen concentrationAlso tested lower concentrations but flow rate similar to no clot at all, not accurateUnable to test whole blood since clots not strong enough to stick to tubeFibrin network forms around RBCs so clot weakened, supported by larger pore size10

Cantilever ApproachMotion driven by solenoidCustom designed silicone cantilevers for increased sensitivitySegmented Photodiode for detectionForce-displacement measurements to approximate tensile modulus

ABCD

JuanIdea based on AFM technology

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Cantilever Design OverviewMOSFET Switch circuit & LABVIEW used to control cantilever movement

LABVIEW used for analysis of signals through DAQ device

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1) Segmented Photodiode

2) Laser Pen

3) Cantilever Holder

4) Cantilever (Aluminum Coating)

5) MOSFET Switch Circuit

6) DAQ

7) 24V Solenoid

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Cantilever Design Images

No lightAmbient LightLaser LightVoltage (V)

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Cantilever Design

Current State: Able to take flat surface measurements

Next Steps: Laser light focusing needed

Cantilever geometry redesign

Increase reflectivity of signal

Juan15

Future WorkIncorporate size-exclusion filter to remove RBCsAdd miniature pressure pump to better control permeationModify conditions to minimize permeation timeTest cantilever design on blood clotsAssess correlation of hemostatic ratio for our tests to fibrinogen concentration

AlbertCurrent permeation time upwards of 20 minutes

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Questions?Thank you!

Albert17