Senior Design Group 11 – Automated Erythrocyte Rheology Sensor

Team AERS: Vandya Juneja, Tim Pham, Vrinda Sant, Edward ShiehAdvisor: Pedro Cabrales

AERS measures the quality of blood based on its deformability

EASY TO OPERATE

FAST 5

mins/test

EFFICIENT1.3mL/test

Problems with Transfusion

Red blood cell (RBC) transfusions carry a risk

• RBC transfusions are associated with increased morbidity and

mortality4

• As red blood cells age in storage, their energy sources are depleted,

weakening their membranes and losing deformability.

• More blood transfusions lead to higher mortality rates while increasing

the length of stay in hospitals due to the need for repetitive

transfusions.

• Currently, the only control for blood quality is the age of the blood.

There is no quantitative test for quality.

Problems with Transfusion

0.0767123287671233 5

Not transfused

Transfused

Not transfused; 15%

Not transfused; 7%

Transfused; 29%

Transfused; 15%

Transfusion Related MortalityNot transfused Transfused

Years after transfusion

Per

cent

age

Mor

talit

y

Automatic Erythrocyte Rheology Sensor

Deformability

❑ RBCs (6-8um) need to be deformable to make their way

through small capillaries (smallest in humans ~4um)

❑ Deformability is a property maintained by complex

biochemical activity

❑ When cells lose deformability, they are destroyed by

macrophages

❑ If non-deformable cells are not eliminated, they may adhere

to blood vessel walls & clog them Storage Time

Deformability

Principle and Methodology

Filter

Motor

Plunger

3 Flow Rates

10% Hct

Principle: AERS measures the pressure across a 5um filter exerted by flow of RBCs

Storage Time

Deformability

Harder for RBCs to pass through filter

pores

Initial Pressure Rise @ each flow

rate

Relative ResistivityTime Constant,

‘𝛃’ 𝜏p

Parameters Computed

Pressure Response

Initial Pressure Rise = Pi

PiPi

Flow 1 Flow 2 Flow 3

Relative Resistivity, ‘ ’𝛃𝛃: Measure of comparative resistance of flow past the filter by a blood sample w.r.t. that of buffer alone

i = RBC, o = buffer; Pi/o = initial pressure rise during a flowhyPi/o = hydrostatic pressure rise between flows; Pbi/o= base pressure before flow V = Mean corpuscular volume/Filter pore volume; h = hematocrit

Initial Pressure Rise

= Pi

PiPi

Flow 1 Flow 2 Flow 3

BloodBuffer

LabVIEW interface with MATLAB for Data Processing

with above Eqn

Validation Testing for ‘ ’𝛃Subjects- Hamster RBCs artificially hardened with 0.008% (m/m) Glutaraldehyde (GA) treatment

Increasing Hardness of

Cells

Increasing Hardness of

Cells

Artificial Hardening

Deformability

Harder for RBCs to pass through

filter pores

Initial Pressure Rise @ each flow rate

Relative Resistance to

flow

Ramp side Decay side

Motor StartMotor Stop

Membrane Filter

Flow RateRBC Deform

ability

Syringe Pump

V

Time Constant AnalysisStep input flow rate Step voltage input

AERS Response

Pressure output from AERS similar to behavior of an RC circuit

Circuit Response

Ramp side

Decay side

Low Pressure

Middle Pressure

Average High Pressure

τp

Low Pressure

Average High Pressure

Middle Pressure

τp

Time Constant Analysis𝜏p: Time taken to reach 50% of maximum initial pressure rise

Time Constant ValidationA: Hamster blood

artificially aged with GA B: Naturally Aged Porcine Blood

𝜏pNot significantly affected by flow rateSensitive to cell hardening (artificial & natural)

Time taken for RBCs to pass through poresDeformability

Hardware Parts Cost

Leadscrew $13

Linear Bearings $44.28

Leadscrew nut $20

Other small fasteners $20

Alignment Shaft $7.88

Shaft coupling $20.11

Syringe $37.50

Mounted Ball bearing $8

1kg PLA 3D Printer Filament $30

Electronic Parts

Arduino $12

BIOPAC $500

Computer $150

Software

Labview $5000

MATLAB $150

TOTAL $5982.77

Current Costs

Hardware Parts ~ $250BIOPAC ~ $500Computer ~ $150Software ~ $5200Total ~ $750

Man hours ~ 300hrs

Successes

✓ Statistical tests show that 𝛃 and 𝜏p are sensitive & accurate parameters

✓ AERS is able to quantify blood quality in the form of graphical

relationships

✓ Only 1.3mL of 350cc (usual amount in blood bag) required for testing

✓ Automated computations

✓ Easy to Operate – Intuitive user interface, simple set-up

✓ High program efficiency & accuracy in picking points for pressure

✓ Fast => 5min/test – necessary for surgical/ emergency settings

EASY TO OPERATE

FAST 5

mins/test

EFFICIENT1.3mL/test

● Automation- Syringe loading and blood dilution- 1-step calculation of deformability scores

Phase 2Future Directions

● Efficient Re-design- Hardware vibration dampening = less digital filters = MORE ACCURACY- Syringe pump design to eliminate dead space

+ Lead screw length- Cartridge

● Testing - Human testing with human blood - Clinical Trials

¤ Automation & Efficient Re- Design ➔ Materials & Parts➔ Programming (man hours)➔ Troubleshooting & validation (animal blood testing)

$8,525¤ Testing ➔ Human Blood

$2400

Item Cost

Human Blood (4 bags) $2400

Programming (labor) $360

Optimization of Design $5800

Animal blood $1000

Consumables $540

Spare parts to redo pump $300

Filter holders $15

Filters $125

Syringes $25

Electronic Parts $360

Total: $10,925

Cost for Phase 2 ~ $11,000

• Current Tech: Laboratory ektacytometers/ rheometers in $10000 – 50000 range3

• Low throughput

• AERS is high throughput

• $70.40/pump = Lucrative on a large scale• financially viable for hospitals• can be used widely in all hospitals

Cost for Mass Production (10000 Units)~ $70.40/pump

EASY TO OPERATE

FAST 5

mins/test

EFFICIENT1.3mL/test

AERS belongs in every hospital

Total Cost Number of parts Cost/part

Glass Syringes $11000 10000 $1.10Plastic Parts (injection molding) $52473 40000 $0.76

Leadscrew $100000 10000 $10

Linear Bearings $7000 20000 $0.35

Leadscrew nut $2000 10000 $0.20Other small fasteners $6000 120000 $0.05

Alignment Shaft $2000 40000 $0.05

Shaft coupling $11000 10000 $1.10Mounted Ball bearing $11000 10000 $1.10

Arduino $1500 10000 $0.15

DAQ Board $500000 10000 $50

Total: $703973 10000 $70.40/pump

Societal and Global Impact ★ Hospitals

■ Patients ● lower cost of transfusions if they have just ONE safe transfusion● lower risk of infection from multiple transfusions, and/or death

■ Doctors/ Nurses● fewer patients needing assistance due to failed transfusions

★ Blood banks■ Donors

● better use of their blood if it is tested with AERS and deemed viable since it is deformable

■ Blood banks itself● will have a higher store of high quality blood, ready for transfusion as a

result of constant monitoring using AERS

★ Regulatory Bodies■ FDA

● develop quantitative measures for RBC quality, storage, purification, and transfusion procedures

References

1. Balakar, N. (2013, March 11). The Shelf Life of Donor Blood. New York Times. Retrieved October 18, 2015

2. Mailo, Shawn R. Storage Time and Interdonor Variability's Effect on Red Blood Cell Storage Lesion. ProQest. gradworks.umi.com/15/83/1583239.html

3. Baskurt, O. K. (2007). Handbook of hemorheology and hemodynamics. Amsterdam: IOS Press. Pages 250 – 251

4. Daurat,G. Specific Hazards of Transfusion in Medical units

Acknowledgements

This project was made possible under the guidance of Dr. Pedro Cabrales, Shawn Mailo & Alex

Williams, and with help from Vivek Jani.

Shout out to Teryn and Asimina for their unrelenting support to the 187 class.

Questions